WO2001047889A1 - Tricyclic compounds - Google Patents

Abstract

Novel tricyclic compounds of general formula (I) or pharmacologically acceptable salts thereof, exhibiting leukotriene antagonism, wherein R1 is halogeno or the like; R2 is nitro or the like; A is a group derived from a five- or six-membered aromatic heterocycle containing 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, or the like; B is -OCH¿2?- or the like; X is sulfur or the like; Y is C1-10 alkylene which may be substituted with halogeno or the like; Z is optionally protected carboxyl or the like; ---- represents a single or double bond; m is an integer of 1 to 4; and n is an integer of 1 to 3.

Description

 Specification

 ; Ring compounds

Besides leukotrienes invention potent leukotriene 13 ₄ antagonism (: ₄ antagonism and leuco Triester E ₄ have antagonism, a pharmacologically acceptable antiallergic agents and useful tricyclic compound or its as anti-inflammatory agents Background art

As a compound having a leukotriene D ₄ antagonistic activity similarly to the present invention and having a structure similar to the compound of the present invention, for example, a compound described in WO 94/19345 is known. As a compound having a partially similar structure, 5- [3- [3- (2-quinolinylmethoxy) phenoxy] propyl] -11H-tetrazole (RG7112; J. Med. C) he m., 33.1 1 8 6 (1900)) or 5 — [[2 — [[4- (2-quinolinylmethoxy) phenoxy] methyl] phenyl] methyl] 1 H-tetrazo-one Compounds (RG12525; J. Med. Chem., 33, 1194 (1990)) and WO95 / 18107. Etc. are known.

With the present invention has a potent leukotriene 1) ₄ antagonism, leukotrienes (: for Synthesis and pharmacological effects of a compound having antagonistic action against ₄ and mouth Ikotoryen E _4, it was studied for many years the results, novel tricyclic compounds have excellent leukotriene 13 ₄ antagonism, and Roy co preparative Lien (: ₄ and with also having well-balanced leuco preparative Lien £ ₄ antagonism, excellent oral absorption and action The present invention was found to have sustainability, and the present invention was completed.

General formula (I)

式中、 R¹は水素原子、 ハロゲン原子、 水酸基、 ニトロ基、 シァノ基、 力ルバモイル基、 ホルミル基、 カルボキシ基、 C ,— C₄アルコキシカルボニル基、 1 H—テトラゾール一 5—ィル基、 一 C₄アルキル基、 フルォロ C,— C₄アルキル基、 ヒ ドロキシ 一 C₄ アルキル基、 C₂— C₄アルケニル基、 C₂— C₄アルキニル基、 C^— C₄アルコキシ基、 フルォロ C ,一 C₄アルコキシ基、 C ,— C₄アルキルチォ基、 Ci— C₄アルキルスルフィ ニル基又は C！— C₄アルキルスルホ二ル基を示し、 R²は水素原子、 ハロゲン原子、 二 トロ基、 シァノ基、 C 一 C₄アルキル基又は C ,一 C₄アルコキシ基を示し、 Aは， 原子、 酸素原子及び硫黄原子から成る群より選択されるへテロ原子を 1乃至 3個を含む 5員若しくは 6員の複素芳香環基又はこれらの複素芳香環基とベンゼン環とが縮合した 複素芳香縮合環基を示し、 該複素芳香環基又は複素芳香縮合環基は置換基として、 ハロ ゲン原子、 ニトロ基、 シァノ基、 Ct— C₄アルキル基、 フルォロ C,— C₄アルキル基、 C i— C アルコキシ基、 フルォロ C ,—。 アルコキシ基、 C !— C^アルキルチォ基、 フ ル才ロ C ,一 C₄アルキルチオ基又は C₃— C₄アルキレン基を有していても良く、 Bは 式— OCH₂—、 式— CH₂CH₂—、 式— SCH₂—、 式— C H ₂0—又は式 _ C H ₂ S— を示し、 Xは酸素原子、 硫黄原子、 メチレン基又は式 =CH—を示し、 Yは、 置換基と してハロゲン原子、 d— C₄アルキル基若しくは C i— C₄アルコキシ基を有していても よい C ,— C ,。アルキレン基、 フヱニレン基又は式 （a) 基：

式中、 o、 pは各々 0乃至 2の整数を示し、 qは 1乃至 4の整数を示す、 を示し、 Zは保護されていてもよいカルボキシ基、 1 H—テトラゾ一ル一 5—ィル基； 式— S0₃H基；式— NH— S0₂— R³；又は式— CO— NH— SO ₂— R³

In the formula, R ¹ is a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a carboxy group, a C, —C ₄ alkoxycarbonyl group, a 1 H-tetrazole-15-yl group, C ₄ alkyl group, fluoro C, —C ₄ alkyl group, hydroxy 1 C ₄ alkyl group, C ₂ —C ₄ alkenyl group, C ₂ —C ₄ alkynyl group, C ^ —C ₄ alkoxy group, fluoro C, One C ₄ alkoxy group, C, — C ₄ alkylthio group, Ci—C ₄ alkylsulfinyl group or C! — C ₄ alkylsulfonyl group, R ² is hydrogen atom, halogen atom, Represents a toro group, a cyano group, a C 1 -C ₄ alkyl group or a C, 1 C ₄ alkoxy group, and A contains 1 to 3 hetero atoms selected from the group consisting of atoms, oxygen atoms and sulfur atoms A 5- or 6-membered heteroaromatic ring group or a heteroaromatic condensed ring group in which these heteroaromatic ring groups are condensed with a benzene ring, wherein the heteroaromatic ring group or the heteroaromatic condensed ring group is a halogen atom; Atom, nitro group, cyano group, Ct—C ₄ alkyl group, fluoro C, —C ₄ alkyl group, C i—C alkoxy group, fluoro C, —. Alkoxy groups, C -! May have a C ₄ alkylene group, B is the formula - - C ^ Arukiruchio group, full Rusairo C, one C ₄ alkylthio group or a C ₃ OCH ₂ -, wherein - CH ₂ CH ₂ —, formula — SCH ₂ —, formula — CH ₂₀ — or formula _ CH ₂ S—, X represents an oxygen atom, a sulfur atom, a methylene group or the formula = CH—, and Y represents a substituent , —C, which may have a halogen atom, a d—C ₄ alkyl group or a C i —C ₄ alkoxy group. Alkylene group, phenylene group or formula (a) group:

In the formula, o and p each represent an integer of 0 to 2, q represents an integer of 1 to 4, and Z represents an optionally protected carboxy group, 1 H-tetrazole-1-yl. Le radical; formula - S0 ₃ H group; formula - NH- S0 ₂ - R ^3; or the formula - CO- NH- SO ₂ - R ³

In the formula, R ³ represents a C! —C ₄ alkyl group, a fluoro C t —C ^ alkyl group or a halogen atom as a substituent, a c, —C ₄ alkyl group, a fluoro C, —C ₄ alkyl group, : ₄ § alkoxy group, a Furuoro C i one C ₄ alkoxy group, at least one of which may have a substituent Fuweniru group selected Ri by the group consisting of nitro and Shiano group, a single bond or Indicates a double bond

And m represents an integer of 1 to 4, and when m is 2 or more, R ¹ may be different, n represents an integer of 1 to 3, and when n is 2 or more, R ² represents A tricyclic compound represented by the following formula or a pharmacologically acceptable salt thereof. BEST MODE FOR CARRYING OUT THE INVENTION

In the compound represented by the general formula (I), the halogen atom for R ¹ includes, for example, a fluorine, chlorine, bromine or iodine atom, preferably a fluorine, chlorine or bromine atom, and more preferably And a fluorine or chlorine atom, particularly preferably a fluorine atom.

The C! —C ₄ alkoxycarbonyl group for R ¹ includes, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl and t-butoxycarbonyl groups. And preferably methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl or Is an isopropoxycarbonyl group, more preferably a methoxycarbonyl or ethoxycarbonyl group, and particularly preferably a methoxycarbonyl group.

The C 1 -C ₄ alkyl group for R ¹ includes a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or t-butyl group, preferably a methyl, ethyl, propyl or isopropyl group. And more preferably a methyl or ethyl group, particularly preferably a methyl group.

Examples of the fluoro C i— C, alkyl group of R ¹ include, for example, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2, 2, 2, 2-trifluoroethyl, 2-fluoropropyl, and 3-fluoropropyl Or 4 monofluorobutyl groups, preferably a fluoromethyl, difluoromethyl, trifluoromethyl or 2-fluoroethyl group, more preferably a fluoromethyl, difluoromethyl or trifluoromethyl group, particularly preferably, It is a difluoromethyl or trifluoromethyl group.

Examples of the hydroxy C i—C ^ alkyl group of R ¹ include hydroxymethyl, 1-hydroxyshethyl, 2-hydroxyl, 1-hydroxyl 1-methylethyl, 1-hydroxyl pill, and 2-hyl. Hydroxypropyl, 3-hydroxypropyl, 1-hydroxybutyl or 4-hydroxybutyl group, preferably, hydroxymethyl, 1-hydroxyxethyl, 2-hydroxyxyl, 1-hydroxy-11-methylethyl, A 1-hydroxypropyl or 2-hydroxypropyl group, more preferably a hydroxymethyl, 1-hydroxyl, 1-hydroxyl-methylethyl or a 1-hydroxypropyl group, particularly preferred. Alternatively, it is a hydroxymethyl or 1-hydroxy-1-methylethyl group.

Examples of the C ₂ -C ₄ alkenyl group for R ¹ include vinyl, 1-propenyl, aryl, isobrodinyl, 1-butenyl, 2-butenyl, 3-butenyl, and 1-methyl-1-pro-propyl. Benzyl, 2-methyl-1 monopropyl or 2-methyl-2-propyl group, preferably vinyl, 1-propyl, aryl, 1-butenyl, 2-butenyl or 2-methyl-1-. It is a propyl group, more preferably a vinyl, 1-propenyl or aryl group, particularly preferably a vinyl group.

The C ₂ -C ₄ alkynyl group for R ¹ includes, for example, ethynyl, 1-propynyl, propargyl, 1-butynyl, 2-butynyl or 3-butynyl group, preferably ethynyl, 1-propynyl or 1-butynyl group. A butynyl group, more preferably an ethenyl or 1-propynyl group, and particularly preferably an ethynyl group.

The C ¹ , 1C ₄ alkoxy group for R ¹ includes, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy or t-butoxy group, preferably methoxy, ethoxy , A propoxy or isopropoxy group, more preferably a methoxy or ethoxy group, and particularly preferably a methoxy group.

Examples of the fluoro C, — C ₄ alkoxy group of R ¹ include fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy, 2,2,2-trifluoroethoxy, 2-fluoropropoxy, and 3 —Examples include fluoropropoxy or 4-fluorobutoxy groups And is preferably a fluoromethoxy, difluoromethoxy, trifluoromethoxy or 2-fluoroethoxy group, more preferably a fluoromethoxy, difluoromethoxy or trifluoromethoxy group, and particularly preferably a difluoromethoxy or trifluoromethoxy group.

Examples of the C ¹ , 1 C ₄ alkylthio group for R ¹ include methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, sec-butylthio or t-butylthio group, and preferably methylthio, ethylthio, propylthio or It is an isopropylthio group, more preferably a methylthio or ethylthio group, and particularly preferably a methylthio group.

Examples of the C 1, 1C ₄ alkylsulfinyl group for R ′ include a methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, and t-butylsulfinyl group. Preferably, it is a methylsulfinyl, ethylsulfinyl, propylsulfinyl or isopropylsulfinyl group, more preferably, a methylsulfinyl or ethylsulfinyl group, and particularly preferably, a methylsulfinyl group.

Examples of the C, — C ₄ alkylsulfonyl group for R ′ include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl and t-butylsulfonyl groups, and are preferred. Is a methylsulfonyl, ethylsulfonyl, propylsulfonyl or isopropylsulfonyl group, more preferably a methylsulfonyl or ethylsulfonyl group, and particularly preferably a methylsulfonyl group.

In particular, R ¹ in the general formula (I) is preferably a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a hydroxyl group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a carboxy group, or a methoxycarbonyl group. , Ethoxycarbonyl group, propoxycarbonyl group, isopropoxyl propyl group, 1H-tetrazole-15-yl group, methyl group, ethyl group, propyl group, isopropyl group, fluoromethyl group, difluoromethyl group, Trifluoromethyl group, 2-fluoroethyl group, hydroxymethyl group, 1-hydroxyxyl group, 2-hydroxyxyl group, 1-hydroxyl 1 methylethyl group, 1-hydroxypropyl group, 2-hydroxypropyl group , Vinyl, 1-propenyl, aryl, 1-butenyl, 2-butenyl, 2- Methyl-1-propenyl group, ethynyl group, 1-propynyl group, 1-butenyl group, methoxy group, ethoxy group, propoxy group, isopropoxy group, fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group , 2-fluoroethoxy, methylthio, ethylthio, propylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, methylsulfonyl, ethylsulfonyl, propylsulfonyl or propylsulfonyl Isopropyl sulphonyl group,

More preferably, a hydrogen atom, a fluorine atom, a chlorine atom, a hydroxyl group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a methoxycarbonyl group, an ethoxycarbonyl group, and a 1H-tetrazo 5-yl, methyl, ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, 1-hydroxyl, 1-hydroxyl-methylethyl, 1-hydroxylpropyl, Vinyl group, 1-propenyl group, aryl group, ethynyl group, 1-propynyl group, 1-butynyl group, methoxy group, ethoxy group, fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, methylthio group , An ethylthio group, a methylsulfinyl group, an ethylsulfinyl group, a methylsulfonyl group or an ethylsulfonyl group, and still more preferably a hydrogen atom, a fluorine atom, a nitro group, a cyano group, a formyl group, a methoxycarbonyl group, 1 H-tetrazole-5-yl group, methyl group, difluorome A tyl group, a trifluoromethyl group, a hydroxymethyl group, a 1-hydroxyl-1-methylethyl group, a vinyl group, an ethynyl group, a methoxy group, a difluoromethoxy group, a trifluoromethoxy group, a methylthio group, a methylsulfinyl group or a methylsulfonyl group. ,

 Particularly preferred are a hydrogen atom, a fluorine atom, a cyano group, a trifluoromethyl group and an ethynyl group.

In the general formula (I), the halogen atom of R ² , a C 1, —C ₄ alkyl group and a C i—C alkoxy group each have the same meaning as described in R ¹ above, and R ² is preferably A hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a nitro group, a cyano group, a methyl group, an ethyl group, a propyl group, an isopropyl group, a methoxy group, an ethoxy group, a propoxy group or an isopropoxy group, more preferably , A hydrogen atom, a fluorine atom, a chlorine atom, a nitro group, a cyano group, a methyl group, an ethyl group, a methoxy group or an ethoxy group, and still more preferably a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group or a methoxy group. And particularly preferably a hydrogen atom.

 In the general formula (I), a 5- or 6-membered heteroaromatic ring group containing 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom represented by A or a heteroaromatic group thereof Examples of the condensed heteroaromatic ring group in which a ring group and a benzene ring are condensed include, for example, a 5-membered heteroaromatic ring such as furan, thiophene, oxazole, thiazole, imidazole, pyrazole or thiadiazole. Groups; 6-membered complex aromatic ring groups such as pyridine, pyrimidine, pyridazine or pyrazine; or heteroaromatic groups such as benzofuran, benzothiophene, benzoxazole, benzothiazole, benzimidazole, quinoline, quinazoline or quinoxaline groups. A fused ring group,

 Preferably, it is an oxazole, thiazole, imidazole, pyrazol, thiadiazol, pyridine, pyrimidine, pyridazine, pyrazine, benzoxazol, benzothiazole, benzimidazole, quinoline, quinazoline or quinoxaline group. It is a thiazole, thiadiazole, pyridine, pyrimidine, benzoxazole, benzothiazole, quinoline or quinazoline group, particularly preferably a pyridine, benzothiazole or quinoline group.

The heteroaromatic ring group or the condensed heteroaromatic ring group may have a substituent. Examples of the substituent include a halogen atom having the same meaning as R ¹ , a nitro group, a cyano group, and a R ¹ having the same meaning. C, — C ₄ alkyl group, fluoro C, — having the same meaning as R ¹ . Alkyl group, C with the same meaning as R ¹ ! One C ₄ alkoxy group, A fluoro C i-C ₄ alkoxy group having the same meaning as R ′, a C 1-C ₄ alkylthio group having the same meaning as R ¹ , or a C ₃ -C ₄ alkylene group such as trimethylene or tetramethylene group (the alkylene group is Bonds with adjacent carbon atoms on the aromatic ring to form a 5- or 6-membered ring)

 Preferably, fluorine, chlorine, bromine, nitro, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, methoxy, ethoxy, propoxy, isopropoxy , Fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy, methylthio, ethylthio, propylthio, isopropylthio, trimethylene or tetramethylene;

 More preferably, fluorine, chlorine atom, nitro, cyano, methyl, ethyl, isopropyl, t-butyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, methylthio, methylthio A thio, trimethylene or tetramethylene group, still more preferably a fluorine, chlorine atom, nitro, cyano, methyl, isopropyl, t-butyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, methylthio or tetramethylene group And particularly preferably a fluorine, chlorine atom, trifluoromethyl or tetramethylene group.

 The number of substituents on the heteroaromatic ring group or the condensed heteroaromatic ring group is from 1 to 4, preferably from 1 to 2.

As A in the general formula (I), specifically, preferably, 2-oxazolyl, 2-thiazolyl, 2- or 4-imidazolyl, 3-pyrazolyl, 1,3,4-thiadiazol-2-y , 2-pyridyl, 2- or 4-pyrimidinyl, 3-pyridazinyl, 2-pyrazinyl, 2-benzoxazolyl, 2-benzothiazolyl, 2-benzimidazolyl, quinolin-1-yl, quinazoline _ 2 —Yl, quinoxaline-1 2 —yl, quinolizine-1 3 —yl, 4-methyl-12-thiazolyl, 4 —ethyl-2 thiazolyl, 4 —isopropyl— 2 —thiazolyl, 4-t —butyl— 2 —thiazolyl , 4_Trifluoromethyl-1-2 thiazolyl, 5-Methyl-1,3,4-Thiadiazol-2-yl, 5-Ethyl-1-1,3,4—Thiadiazol-2-yl, 5-isopropyl One, 3,4-thiadiazol-2-yl, 5-t-butyl-1,3,4-thiadiazol-2-yl, 5-trifluoromethyl-1,3,4—thiadiazol 2'-yl, 5, 6-difluoro-2-pyridyl, 5,6-dichloro-2- (pyridyl), 5,6-dimethyl_2-pyridyl, 5, 6-jetyl-2-pyridyl, 6_trifluoro Lomethyl-2-pyridyl, 6-methylthio-1-pyridyl, 5,6-dihydrocyclopenta [b] pyridine-12-yl, 5,6,7,8-tetrahydroquinoline-12-yl, 5, 6-difluoro-2-pyrimidinyl, 5,6-dichloro-1-2-pyrimidinyl, 5,6-dimethyl-2-pyrimidinyl, 6-trifluoromethyl-12-pyrimidinyl, 5,6-dihydrocyclopenta [d] pyri Midin-1 2 — yl, 5, 6, 7, 8 — tetrahydroquinazolid 1-2-yl, 6-fluoro-2-benzoxazolyl, 5-fluoro-2-benzoxazolyl, 5,6-difluoro- 2 benzoxazolyl, 6 — benzoxazolyl, 5 — benzoxazolyl, 5 — benzoxazolyl, 5, 6 —dichloro-2-benzobenzoxazolyl, 5 _ mouth 1 6-Fluoro-2-benzoxazolyl, 5-methyl-2-benzoxazolyl, 5-cyano 2-benzoxazolyl, 5—Trifluoromethyl 1-2-benzoxoazolyl, 5-methylthio-1-benzobenzoxazolyl , 6-Fluoro-2-benzothiazolyl, 5-Fluoro-2-benzothiazolyl, 5,6-Difluoro-2-benzothiazolyl, 6-Chloro-2-benzothiazolyl, 5-Chloro-2-benzothiazolyl, 5,6-Dichloro Mouth 2 — benzothiazolyl, 5 — Methyl 6 — Fluoro-2 — benzothiazolyl, 5 — Methyl 1 — benzothiazolyl, 5 — Cyanone 2 — benzothia Ryl, 5-trifluoromethyl_2-benzothiazolyl, 5-methylthio-2-benzothiazolyl, 5-fluoroquinoline-2-yl, 6-fluoroquinolin-2-yl, 7_fluoroquinolin-12-yl , 5-chloroquinoline 1-2 -yl, 6-chloroquinoline 1-2-yl, 7-chloroquinoline 1-2-yl, 7-methylquinoline 1-2-yl, 7 _ trifluoromethylquinoline 1- 2 -yl, 7-methoxyquinoline 1-2-yl, 7-difluoromethoxyquinoline _ 2-yl, 7-trifluoromethyloxyquinoline 1-2-yl, 5, 7-difluoroquinoline 1 2 _Yl, 6,7-difluoroquinoline-1-yl, 5,7-dichloroquinoline-2-yl, 6,7-dichloroquinoline-1-yl, 5-chloro-1,7 —Fluoroquinoline 2—yl, 6 —Black mouth 7—Fluoroki Phosphorus one 2 - I le, 7-Clos port one 5- Furuorokinorin one 2 - I le, 7- chloro 6- Furuorokinorin one 2 _ I Le, 7-black opening one

6 — cyanoquinoline 2 — yl, 7 — cyano 6 — fluoroquinoline 1 2 _yl, 6 — fluoro 7 — trifluoromethylquinoline 1 2 — yl, 5, 6, 7-trifluoroquinoline 1

2 — yl, 5 — Fluoroquinazoline 1 — 2 — yl, 6 — Fluoroquinazoline 1 — 2 _yl, 7 — Fluoroquinazoline 1 — 2-yl, 5 — Black mouth quinazoline 1 — 2 6-Black quinazoline-1-yl, 7-Chloroquinazoline_2_yl, 7—Methylquinazoline-1-yl, 7—Trifluoromethylquinazoline 1-2-yl, 7— Methoxyquinazoline-1-yl, 7-difluoro methoxyquinazoline-2-yl, 7-trifluoroquinoxyquinazoline_2-yl, 5,

7-difluoroquinazoline-1-yl, 6,7-difluoroquinazoline-2-yl, 5,7-dichloroquinazoline-1-yl, 6,7-dichloroquinazoline-1-yl , 5-chloro-7-fluoroquinazoline-1-yl, 6-chloro-7-fluoroquinazoline-1-2-yl, 7-chloro-5-fluoroquinazoline-1-yl, 7- Chloro 6-Fluoroquinazoline 1-2-yl, 7-Chloro 6-Cyanokinazoline 1-2-yl, 7-Cyano 1-6-Fluoroquinazoline 1-2-yl, 6-Fluoro 7- A trifluoromethylquinazoline-1-yl or a 5,6,7-trifluoroquinazoline-12-yl group, more preferably 2-thiazolyl, 1,3,4-thiadiazo-2-yl; 2-pyridyl, 2-pyrimidinyl, 2-benzoxazolyl, 2-benzothiazolyl, Norin-1-yl, quinazoline-12-yl, 4-methyl-12-thiazolyl, 4-isopropyl-12-thiazolyl, 4-t-butyl-2--2-thiazolyl, 4-trifluoromethyl-2-thiazolyl, 5-Methyl-1,3,4-thiadiazole-1-yl, 5-isopropyl-1,3,4-thiadiazol-2-yl, 5_t-butyl-1,3, 4-thiadiazole-l- 2-yl, 5- trifluoromethyl-1,3,4-thiadiazol-2-yl, 5,6-difluoro-2-pyridyl, 5, 6-dichloro-2-pyridyl, 5,6 -Dimethyl-1-pyridyl, 5, 6-dihydrocyclopenta [b] pyridine-12-yl, 5,6,7,8-tetrahydroquinoline-12-yl, 5,6-difluoro-2-pyrimidinyl, 5 , 6-Dichloro-2-pyrimidinyl, 5, 6-Dimethyl-12-pyrimidinyl, 6-Trifluoromethyl-1-pyrimidinyl, 5,6-Dihydrocyclopenta [d] pyrimidine-12-yl, 5,6, 7,8-tetrahydroquinazoline-1-yl, 6-fluoro-2-benzobenzozolyl, 5-fluoro-2-benzoxazolyl, 5,6-difluoro-2-benzoxazolyl, 6-cyclo-2-benzo Oxazolyl, 5-chloro-2-benzobenzozolyl, 5, 6-dichloro-12-benzoxazolyl, 5-chloro-6-fluoro-2-benzobenzozolyl, 5-methyl-2-benzobenzozolyl, 5- Cyan-2-benzobenzoazolyl, 5 _trifluoromethyl-12-benzoxazolyl, 5-methylthio-1-benzobenzoazolyl, 6-fluoro-2-benzothiazolyl, 5-fluoro-2-benzothiazolyl, 5, 6-difluoro-2-benzothiazolyl, 6-chloro-2-benzothiazolyl, 5-chloro-2-benzothiazolyl, 5, 6-dichloro-2-benzothiazolyl, 5-chloro-6-fluoro-2-benzothiazolyl, 5-methyl-1-2 —Benzothiazolyl, 5 —cyanone 2 —benzothiazolyl, 5-trifluoromethyl-2-benzoicia Zolyl, 5-methylthio-1-benzobenzoyl, 5-fluoroquinoline-1-yl, 6_fluoroquinoline-1-yl, 7-fluoroquinoline-2-yl, 5-chloroquinoline-1-yl , 6 — Clonoquinoline 1-2-yl, 7-Clonoquinoline 1-2 -yl, 7-Methylquinoline 1-2 -yl, 7 _ trifluoromethylquinoline 1-2-yl, 7-Methoxy Quinoline 1-2-yl, 7-difluoromethoxyquinoline-1-2-yl, 7 _ trifluoromethyloxyquinoline-1-2-yl, 5, 7-difluoroquinoline-1-2-yl, 6, 7-difluoro Quinoline 1 2 —yl, 5,7-Dichloroquinoline 1 2 —yl, 6,7—Dichloroquinoline 1 2 —yl, 5 _Black mouth _ 7 —Fluoroquinoline 1 2 —yl, 6—Black mouth 1 7—Fluoroquinoline 2—Ill, 7—Black mouth 1—Fluoroquino 1-yl, 7-chloro-6-fluoroquinoline 1-2-yl, 7-chloro-6-cyanoquinoline 1-2-yl, 7-cyano 6-fluoroquinoline 1-2-yl, 6-fluoro-7- Trifluoromethin quinolinone 2-yl, 5, 6, 7 _ trifluoroquinoline 1-2 — yl, 5 — Fluoroquinazoline 2 — yl, 6 — Fluoroquinazoline 1-2 — yl, 7 — Fluoro Quinazoline-1-yl, 5—black quinazoline 1-2—yl, 6—black quinazoline 1-2—yl, 7-chloroquinazolin-2-yl, 7-methylquinazoline_2—yl, 7— Trifluoromethylquinazoline 1-2-yl, 7-methoxyquinazoline_2-yl, 7-difluoromethoxyquinazoline 1-2-yl, 7-trifluoromethylquinazoline_2-yl, 5, 7-difluo Loquinazoline one 2 —Yl, 6, 7—difluoroquinazoline-1-yl, 5, 7—dichloroquinazoline-1-yl, 6,7-dichloroquinazoline-1-2—yl, 5 —cloguchi-7—full Oroquinazoline 1 2 _ yl, 6 — Black mouth 7 — Fluoroquinazoline 1 2 — yl, 7 — Chloro 5 — Fluoroquinazoline 1 2 — yl, 7 — Chloro 6 — Fluoroquinazoline 1 2 —Ill, 7—Black mouth 6—Shia Noquinazoline-1-yl, 7_cyano-1-6-fluoroquinazoline-1-yl, 6-fluoro-7-trifluoromethylquinazoline-1-yl or 5,6,7-Trifluoroquinazoline-1 2-yl group,

 Even more preferably, 2-pyridyl, 2-benzothiazolyl, quinolin-1-yl, 5,6-difluoro-2-pyridyl, 5,6-dichloro-1-pyridyl, 5,6-dimethyl-2-pyridyl , 5,6,7,8-tetrahydroquinoline-1-yl, 6-fluoro-2-benzothiazolyl, 5-fluoro-2-benzothiazolyl, 5,6-difluoro-2-benzothiazolyl, 6-clothazoline Benzothiazolyl, 5-chloro-2-benzothiazolyl, 5, 6-dichloro-12-benzothiazolyl, 5-chloro-6-fluoro-2-benzothiazolyl, 5-methyl-2-benzothiazolyl, 5-cyano 2-benzothiazolyl, 5-trifluoromethyl 2-benzothiazolyl, 5-methylthio-1-benzothiazolyl, 5-fluoroquinoline_2-yl, 6-fluoroquinoline 2-yl, 7-fluoroquinoline 2-yl, 5-black quinoline 2-yl, 6-quinoline 1-2-yl, 7-quinoline 1-2-yl, 7-methyl Quinoline 1-2-yl, 7-Trifluoromethylquinoline 1-2-yl, 7-Methoxyquinoline 1-2-yl, 7-Difluoromethoxyquinoline 1-2-yl, 7-Trifluoromexoxyquinoline 1-2 _Yl, 5,7-difluoroquinoline 1-2 yl, 6,7-difluoroquinoline 1-2-yl, 5,7-dichloroquinoline 1-2-yl, 6,7-dichloroquinoline 1-2 7-Fluoroquinoline 1-2-yl, 6-Chloro 7-Fluoroquinoline 2-yl, 7-Chloro-5-Fluoroquinoline 1-2-yl, 7_Chloro-1 6-Fluoroquinoline 1-2-yl, 7-Chloro 6-Cyanokinoline 1-2-yl, 7-Shia One 6- Furuorokinorin one 2-I le, 6- Furuoro 7 triflate Ruo b methylquinoline one 2- I le or 5, 6, 7-triflate Ruo b quinoline one 2-I group,

 Particularly preferred are 7-fluoroquinoline-12-yl, 7-chloroquinoline-12-yl, 6,7-difluoroquinoline-12-yl, and 6,7-dichloroquinoline-12-yl 7-chloro-6-fluroquinoline-12-yl, 6-fluoro-7-trifluoromethylquinoline-12-yl or 5,6,7,8-tetrahydroquinoline-2-yl group.

In the above general formula (I), B is a formula _OCH ₂ —, a formula —CH ₂ CH ₂ —, a formula SCH ₂ —, a formula —CH ₂₀ — or a formula —CH ₂ S—, preferably a formula — OCH ₂ —, Formula 1 CH ₂ 0 — or Formula 1 CH ₂ CH ₂ —.

 In the general formula (I), X is an oxygen atom, a sulfur atom, a methylene group or a formula = CH-, preferably a methylene group, an oxygen atom or a sulfur atom.

C—C, of Y in the general formula (I). The alkylene group, for example, methylene, E Ji Ren, trimethylene, tetramethylene, pentamethylene, to Kisamechiren, heptamethylene, Okutamechiren, include nonamethylene or decamethylene group, preferably is one c ₅ Al Killen group, further Preferably, it is a methylene, ethylene or trimethylene group, particularly preferably an ethylene or trimethylene group.

The alkylene group may have a substituent, and a halogen atom as the substituent, A C ₄ alkyl group and a C, 1 C ₄ alkoxy group have the same meaning as the above-mentioned halogen atom, a C, 1 C ₄ alkyl group and a 1 C ,, alkoxy group.

 The substituent of the alkylene group of γ is preferably a fluorine, chlorine atom, methyl, ethyl, propyl, methoxy, ethoxy or propoxy group, more preferably a fluorine atom, methyl, ethyl or methoxy group. And particularly preferably a fluorine atom or a methyl group.

 The phenylene group of Y is 1,2-phenylene, 1,3-phenylene or 1,4-phenylene group, preferably 1,2-phenylene or 1,3 phenylene group. —A phenylene group, and more preferably a 1,2-phenylene group.

 The group represented by the formula (a) of Y is preferably a group in which o = 0, p = 0, q = l (hereinafter referred to as (a-1) group), and o = 0, p = 1 , q = l (hereinafter referred to as (a-2) group), o = 0, p = 1, q = 2 (hereinafter referred to as (a-3) group), o = l, = 0, q = l group (hereinafter referred to as (a-4) group), o = l, p = 1, q = l group (hereinafter referred to as (a-5) group), o = l, a group in which p = 1 and q = 2 (hereinafter referred to as (a-6) group) or a group in which 0 = 1, p = 1 and q = 3 (hereinafter referred to as (a-7) group), More preferably, it is a (a_4) group, a (a-5) group or a (a-6) group, particularly preferably a (a-5) group.

 Preferred examples of Y in the general formula (I) include methylene, ethylene, trimethylene, tetramethylene, pentamethylene, fluoromethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, and 1,1- Difluoroethylene, 2,2-difluoroethylene, 1-methylethylene, 2_methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene, 1-methoxethylene, 2 —Methoxyxylene, 1—Fluorotrimethylene, 2-Fluorotrimethylene, 3-Fluorotrimethylene, 1,1-Difluorotrimethylene, 2,2-Difluorotrimethylene, 3,3-Difluorotrimethylene, 1— Methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, 2,2-getyltrimethylene, 2-methoxytrimethylene, 3-methoxytrimethylene, 2,2-dimethytrimethylene, 3, 3-dimethoxytrimethylene, 1,2-phenylene or 1,4-phenylene group, (a-1) group, (a-2) group, (a-3) group, (a-4) group , (A-5) group or (a-6) group;

More preferably, methylene, ethylene, trimethylene, fluoromethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1 difluoroethylene, 2,2-difluoroethylene, 1-methylethylene, 2-methylethylene , 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene, 1-fluorotrimethylene, 2-fluorotrimethylene, 3-fluorotrimethylene, 1,1-difluorotrimethylene, 2, 2-difluorotrimethylene, 3,3-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene Methylene, 1,2-phenylene group, (a-4) group, (a-5) group or (a 6) is a group, Still more preferably, methylene, ethylene, trimethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, 1-methylethylene, 2-methylethylene Methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene, 2,2-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene , 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, 1,2-phenylene group or (a-5) group, particularly preferably methylene, ethylene, trimethylene, 1-methylethylene, 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2 Echiruechiren, 1, 2-phenylene group or a (a_ 5) group.

Z formula - NH- S 0 ₂ - R ³ or the formula -CO- NH- S0 ₂ - In the group represented by R ^3, C of R ^3, - C ₄ alkyl group, Furuoro one C ₄ 7 alkyl group and Fe Ha androgenic, C, is a substituent on the alkenyl group - alkyl, Furuoro C i-C ₄ alkyl, C, - C ₄ alkoxy, Furuoro - C ₄ alkoxy, each halogen atom of said R ^1, C! - It has the same meaning as C ₄ alkyl group, fluoro Ci- ^ alkyl group, C ^ -C ^ alkoxy group, fluoro C, — C ₄ alkoxy group.

R ³ is preferably methyl, ethyl, propyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, phenyl, (0, m or p— ) Fluorophenyl, (0, m or p—) cyclophenyl, (o, m or p—) methylphenyl, (o, m or p—) ethylphenyl, (o, m or p—) (trifluoromethyl ) Phenyl, (o, m or p_) methoxyphenyl, (o, m or p—) ethoxyphenyl, (0, m or p—) (difluoromethoxy) phenyl, (0, m or p—) ( Trifluoromethoxy) phenyl, (0, m or p—) nitro phenyl or (0, m or p—) cyanophenyl group,

 More preferably, methyl, ethyl, trifluoromethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, phenyl, (0 or p—) fluorophenyl, (0 or p—) cyclophenyl, ( (0 or P—) methylphenyl, (0 or p_) (trifluoromethyl) phenyl, (0 or p—) methoxyphenyl, (0 or P—) (difluoromethoxy) phenyl, (0 or p_) (trifluoromethyl) Toxin) phenyl, (0 or p—) nitrophenyl or (0 or P—) cyanophenyl,

 Even more preferably, methyl, ethyl, trifluoromethyl, phenyl, p-fluorophenyl, p-chlorophenyl, (0 or P-) methylphenyl, p- (trifluoromethyl) phenyl, (0 or p- ) Methoxyphenyl, p- (difluoromethoxy) phenyl, p- (trifluoromethoxy) phenyl, p-nitrophenyl or p-cyanophenyl, and particularly preferably methyl, trifluoromethyl, phenyl, 0-methylphenyl or p- is a methylphenyl group.

Preferred groups for Z in the general formula (I), specifically, carboxy, wherein one S0 ₃ H, 1 H- Tetorazoru 5 I le, methanesulfonyl § amino, ethanesulfonyl § Mino, triflumizole Fluoromethanesulfonylamino, phenylsulfonylamino, p —fluorophenylsulfonylamino, p —chlorophenylsulfonylamino, 0 _methylphenylsulfonylamino, p-methylphenylsulfonylamino, p-methylphenylsulfonylamino, p-triflu O-methylphenylsulfonylamino,

0-Methoxyphenylsulfonylamino, p-Methoxyphenylsulfonylamino, p-Difluoromethoxyphenylsulfonylamino, p-Trifluoromethoxyphenylsulfonylamino, p-Nitrophenylsulfonylamino, p-Cyanophenylsulfonylamino, methanesulfonylaminocarbonyl, ethanesulfonylaminocarbonyl, trifluoromethanesulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, p-fluorophenylsulfonylaminocarbonyl, p-Chlorophenyl sulfonyl § amino carbonyl, ₀ _ methyl phenylalanine sulfonyl § amino carbonyl, p - methyl phenylalanine sulfonyl § amino carbonitrile sulfonyl, p- triflumizole Ruo Russia methyl phenylalanine sulfonyl § amino carbonyl, 0-main Tokishifue two pulse Phonylaminocarbonyl, p-methoxyphenylsulfonylaminocarbonyl, p-difluoromethoxyphenylsulfonylaminocarbonyl, p-trifluoromethoxyphenylsulfonylaminocarbonyl, p-ditophenylphenylsulfonylaminocarbonyl or p- A cyanophenylsulfonylaminocarbonyl group,

More preferably, carboxy, wherein one S 0 ₃ H, 1 H- tetrazole one 5 - I le, Metansuru Honiruamino, triflumizole Ruo b methanesulfonyl § Mino, phenylalanine sulfonyl § amino, 0 - methyltransferase phenylalanine sulfonyl § Mino, p —Methylphenylsulfonylamino, methanesulfonylaminocarbonyl, trifluoromethanesulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, 0-methylphenylsulfonylaminocarbonyl or p—methylphenylsulfonylaminocarbonyl group And

Particularly preferred are carboxy, formula —SO ₃ H, methanesulfonylamino, trifluoromethanesulfonylamino, methanesulfonylaminocarbonyl or trifluoromethanesulfonylaminocarbonyl.

When Z is a carboxy group, the carboxy group may be protected with a protecting group. The protecting group is not particularly limited as long as it can be easily deprotected and converted into a carboxy group in a living body. Examples thereof include a C ₄ alkyl group having the same meaning as defined for R ¹ ; benzyl, C ₇ _ C i, such as phenyl Echiru or phenylpropyl group. Aralkyl groups; acetomethyl, 1-acetoxityl, 1-acetoxoxypropyl, 1-acetoxoxybutyl, propanoyloxymethyl, 1-propanoyloxyshetyl, butanoyloxymethyl, 1-butanoyloxy methylation, Viva Roy Ruo carboxymethyl, 1-pivaloyl I Ruo key shell chill, c ₂ such as 1-Viva Roy Ruo propyl or 1 one Viva Roy Ruo carboxybutyl group - substituted with c ₅ alk Noi Ruo alkoxy group C, monoalkyl group; methoxycarbonyloxymethyl, 1- (methoxycarbonyloxy) ethyl, ethoxycarbonyloxymethyl, 1- (ethoxycarbonyloxy) ethyl, propoxycarbonyloxymethyl, isopropoxy Xycarbonyloxymethyl, 1- (isopropoxycarbonyloxy) ethyl, butoxy Carbonyloxymethyl, 1- (butoxycarbonyloxymethyl) ethyl, t-butoxycarbonyloxymethyl or 1- (t-butoxyca Ruponiruokishi) such as Echiru group (c, - c ₄ alkoxy) carbonyl O carboxymethyl C is substituted with a group, one C ,, alkyl group; N, N-dimethyl § amino carbonyl methyl, 2-(N, N-dimethylcarbamoyl Rua iminocarbonyl) Echiru or N, such as N- Jefferies chill § amino carbonyl methyl N, N- di (C, - C ₄ alkyl) § amino substituted by a carbonyl group C ^ - C ^ alkyl group; 2 — (N, N—dimethylamino) ethyl, 2— (N, N—diethylamino) ethyl, 3— (N, N—dimethylamino) propyl, 2-piberidinoethyl, 2— (4-methyl) piberidinoethyl, 3-piperidi N, such as Nopuropiru or 2 Moruhorinoechiru group, N- di (C ^ - C ₄ Aruki Le) Amino group or contain an oxygen atom is substituted with may also be 5 or 6 membered cyclic Amino group C , - C ₄ alkyl group; one It is (5 - methyl one 2 - Okiso one 1, 3 - Jiokisoren one 4 - I le) methylation group.

As the protective groups of carboxy group, preferably, c ^ - c ^ alkyl group, a benzyl group, c ₂ - c ₅ Arca Noi Ruo carboxymethyl C is substituted with a group, -. A 2-alkyl group, a Ci-C ^ alkyl group substituted with a (C ^ -C ^ alkoxy) carbonyloxy group or a (5-methyl-2-oxo-1, 3-dioxolen-1-4-yl) methyl group Yes,

 More preferably, it is a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, acetomethyl, 1-acetoxityl, bivaloyloxymethyl or 1-bivaloyloxymethyl group.

In the general formula (I), m is an integer of 1 to 4, preferably m is 1, 2 or 3, and particularly preferably 1 or 2. When m is 2 or more, R ¹ may be different. In the general formula (I), n is an integer of 1 to 3, preferably n is 1 or 2, and particularly preferably 1. When n is 2 or more, R ² may be different.

 The compound (I) of the present invention may have an optical isomer (including a diastereomer) based on an asymmetric carbon atom in the molecule, or may have a geometric isomer based on a double bond. Isomers are also included in the present invention.

 The compound (I) of the present invention can be converted into a pharmacologically acceptable salt, if necessary. Such salts include acid addition salts of mineral acids such as hydrochloride, hydrobromide, hydroiodide, sulfate or phosphate; trifluoroacetate, methanesulfonate, ethanesulfonic acid Salts, acid addition salts of organic acids such as benzenesulfonate, p-toluenesulfonate, oxalate, maleate, fumarate, tartrate or citrate; sodium, potassium, calcium Metal salts of carboxylic acids such as shim, magnesium, manganese, iron or aluminum salts; or organic bases such as ammonium, triethylamine, guanidine, hydrazine, quinine or cinchonine salts. Pharmacologically acceptable salts such as salts. The compound (I) of the present invention can also exist as a hydrate.

 In the tricyclic compound having the general formula (I) of the present invention, preferably,

(1) R ^{1 of the} compound represented by the formula (I) is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a hydroxyl group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a carboxy group, or a methoxycarbonyl group. , Ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, 1 H-Tetrazol-5-yl, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, hydroxymethyl, 1-hydroxyxethyl , 2-hydroxyethyl, 1-hydroxy 1-methylethyl, 1-hydroxypropyl, 2-hydroxypropyl, bul, 1-propenyl, aryl, 1-butenyl, 2-butenyl group, 2-methyl-1-propenyl group, ethynyl group, 1-propynyl group, 1-butynyl group, methoxy group, ethoxy group, propoxy group, isopropoxy group, fluoromethoxy group, difluoromethoxy group, Trifluoromethoxy, 2-fluoroethoxy, methylthio, ethylthio, propylthio Selected from the group consisting of isopropylthio, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, methylsulfonyl, ethylsulfonyl, propylsulfonyl, and isopropylsulfonyl Tricyclic compounds,

(2). In the compound represented by the formula (I), R ¹ is a hydrogen atom, a fluorine atom, a chlorine atom, a hydroxyl group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a methoxycarbonyl group, an ethoxycarbonyl group, 1 H-tetrazole-5-yl, methyl, ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, 1-hydroxyl, 1-hydroxyl-methylethyl , 1-hydroxypropyl group, vinyl group, 1-probenyl group, aryl group, ethynyl group, 1-propynyl group, 1-butynyl group, methoxy group, ethoxy group, fluoromethyoxy group, difluorome Toxyl group, trifluoromethoxy group, methylthio group, ethylthio group, methylsulfinyl group, ethylsulfinyl group, methyls Honiru Moto及 beauty Echirusuruhoniru are those selected from the group consisting of group tricyclic compounds,

(3). In the compound represented by the formula (I), R ¹ is a hydrogen atom, a fluorine atom, a nitro group, a cyano group, a formyl group, a methoxycarbonyl group, a 1H-tetrazole-1-yl group, a methyl group , Difluoromethyl group, trifluoromethyl group, hydroxymethyl group, 1-hydroxy-1-methylethyl group, vinyl group, ethynyl group, methoxy group, difluoromethoxy group, trifluoromethyl group, methylthio group, methylsulfinyl group and methyl A tricyclic compound selected from the group consisting of sulfonyl groups,

(4). A tricyclic compound wherein R ^{1 of the} compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a cyano group, a trifluoromethyl group and a diethynyl group;

(5). R ^{2 of the} compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a nitro group, a cyano group, a methyl group, an ethyl group, a methoxy group and an ethoxy group. Tricyclic compounds, (6). A tricyclic compound wherein R ^{2 of the} compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group and a methoxy group;

(7). A tricyclic compound in which R ^{2 in the} compound represented by the formula (I) is a hydrogen atom,

(8). In the compound represented by the formula (I), the ring represented by A is furan, thiophene, oxazole, thiazole, imidazole, pyrazolyl, thiadiazole, pyridine, pyrimidine, pyridazine, pyrazine, benzofuran, A tricyclic compound selected from the group consisting of benzothiophene, benzoxazole, benzothiazole, benzimidazole, quinoline, quinazoline and quinoxaline rings;

(9). In the compound represented by the formula (I), the ring represented by A is oxazole, thiazole, imidazole, pyrazole, thiadiazole, pyridine, pyrimidine, pyridazine, pyrazine, benzoxazole, benzothiazole. A tricyclic compound which is selected from the group consisting of benzyl, benzimidazole, quinoline, quinazoline and quinoxaline rings;

(10). The ring represented by A in the compound represented by the formula (I) is selected from the group consisting of thiazole, thiadiazole, pyridine, pyrimidine, benzoxazole, benzothiazole, quinoline and quinazoline rings. Tricyclic compounds,

(11) A tricyclic compound in which the ring represented by A in the compound represented by the formula (I) is selected from the group consisting of pyridine, benzothiazole and quinoline rings;

(12). When the heteroaromatic ring group or the condensed heteroaromatic ring group is fluorine, chlorine, bromine, nitro, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, fluoromethyl, difluoromethyl, trifluoromethyl, At least one selected from the group consisting of dimethyl, 2-fluoroethyl, methoxy, ethoxy, propoxy, isopropoxy, fluoromethoxy, difluoromethoxy, trifluoromethyl, 2-fluoroethoxy, methylthio, ethylthio, propylthio, isopropylthio, trimethylene and tetramethylene. -A tricyclic compound which is substituted by a kind of substituent,

(13). When the heteroaromatic ring group or heteroaromatic condensed ring group is fluorine, chlorine atom, nitro, methyl, ethyl, isopropyl, t-butyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, fluoromethoxy, difluoromethoxy. A tricyclic compound which is substituted by at least one substituent selected from trifluoromethoxy, methylthio, ethylthio, trimethylene and tetramethylene groups; (14). The heteroaromatic ring group or the condensed heteroaromatic ring group is selected from fluorine, chlorine, nitro, cyano, methyl, isopropyl, t-butyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, Tricyclic compounds substituted by at least one substituent selected from methylthio and tetramethylene groups,

(15). A tricyclic compound in which the heteroaromatic ring group or the condensed heteroaromatic ring group is substituted with at least one substituent selected from a fluorine atom, a chlorine atom, a trifluoromethyl group, and a tetramethylene group. (16). In the compound represented by the formula (I), A is 2-oxazolyl, 2-thiazolyl, 2-but 4-imidazolyl, 3-pyrazolyl, 1,3,4-thiadiazolyl —Yl, 2-pyridyl, 2- or 4-pyrimidinyl, 3-pyridazinyl, 2-pyrazinyl, 2-benzozoxazolyl, 2-benzothiazolyl, 2-benzimidazolyl, quinolin-1-yl, quinazoline-1-yl , Quinoxaline-2-yl, quinolidine-1-yl, 4-methyl-2-thiazolyl, 4-ethyl-2-thiazolyl, 4-isopropyl-12-thiazolyl, 4-t-butyl-2- Azolyl, 4 _ triflumizole Ruo Russia methyl one 2-thiazolyl, 5-methyl-1, 3,

4-thiadiazole—2-yl, 5-ethyl—1,3,4-thiadiazol-2-yl, 5-isopropyl-1, 3,4-thiadiazole-2-yl, 5 _t _butyl-1 , 3,4-thiadiazol-2-yl, 5-trifluoromethyl-1,3,4-thiadiazole-1-2-yl, 5,6-difluoro-2-pyridyl, 5,6-dichloro-1 2-pyridyl, 5,6-dimethyl-1-2-pyridyl, 5,6-getyl-2-pyridyl, 6_trifluoromethyl_2-pyridyl, 6-methylthio-1-pyridyl, 5,6-dihydro Cyclopenta [b] pyridine-12-yl, 5,6,7,8-tetrahydroquinoline-12-yl, 5,6-difluoro-2-pyrimidinyl, 5,6-dichloro-12-pyrimidinyl, 5, 6-dimethyl-2-pyrimidinyl, 6-trifluoromethyl-1-pyrimidinyl, 5,6-dihi Drocyclopenta [d] pyrimidin-2-yl, 5,6,7,8-tetrahydroquinazoline-12-yl, 6-fluoro-2-benzobenzoxazolyl, 5_fluoro-2-benzobenzoxazolyl , 5, 6-Difluoro-2-benzoxazolyl, 6-chloro-2-benzobenzoazolyl, 5-chloro-2-benzobenzozolyl, 5,6-dichloro1-2-benzoxazolyl 5-chloro-6-fluoro-2-benzoxazolyl, 5-methyl-2-benzoxazolyl, 5-cyano_2-benzoxazozolyl, 5-trifluoromethyl-1-2-benzoxazolyl , 5-Methylthio-1-benzobenzoazolyl, 6-Fluoro-2-benzothiazolyl, 5-Fluoro-2-benzothiazolyl, 5,6-Difluoro-2-benzothiazolyl, 6-Cro-2-benzothiazolyl,

5-benzo-2-azothiazolyl, 5,6-dichloro-2-benzothiazolyl, 5_chloro-6-fluoro-2-benzothiazolyl, 5-methyl-1-benzothiazolyl, 5-cyano-2-benzothiazolyl , 5-trifluoromethyl-2-benzothiazolyl, 5-methylthio-1-benzothiazolyl, 5-fluoroquinoline-2-yl, 6-fluoroquinoline 2 — yl, 7 _ fluoroquinoline 1 _ 2, 5 — black quinoline 1 _ 2, 6 — black quinoline _ 2 _ yl, 7 — black quinoline 1 2 _ yl, 7 — methyl Quinoline 1-2-yl, 7 _trifluoromethylquinoline 1-2-yl, 7-methoxyquinoline 1-2-yl, 7-difluoro-methoxyquinoline 1-2-yl, 7-trifluorofluoroquinoline 1-2 —Yl, 5, 7—difluoroquinoline 1—2, yl, 6, 7—difluoroquinoline 1—2—yl, 5,7—dichroquinoline—2-yl, 6, 7.— Dichroquinoline 1 2 —yl, 5—Chloro 1 7 —Fluoroquinoline 1 2 —yl, 6 —Chloro 1 7—Fluoroquinoline 1 2 _yl, 7—Chloro 5 —Fluoroquinoline 1 2 —yl , 7 — Black mouth 6 — Fluoroquinoline 1 2 — yl, 7 — Chloro

6 — cyanoquinoline 1-2-yl, 7-cyano 6 _ fluoroquinoline 1-2-yl, 6 — fluoro 7-trifluoromethylquinoline 1-2-yl, 5, 6, 7-trifluoroquinoline 1

2 _yl, 5 — Fluoroquinazoline 1 2 _yl, 6 — Fluoroquinazoline 1 2 — yl, 7 — Fluoroquinazoline 1 2 — yl, 5 — Black mouth quinazoline 1 2 _ 7-Black quinazoline 1-2-yl, 7-Methylquinazoline 1-2-yl, 7-Trifluoromethylquinazoline 1-2-yl, 7— Methoxyquinazoline-1-yl, 7-difluoro methoxyquinazoline 1-2-yl, 7-trifluoroquinoxyquinazoline-1-yl, 5,

7-difluoroquinazoline-l-yl, 6,7-difluoroquinazoline-l-yl, 5,7-dichloroquinazoline-l-yl, 6,7-dichloroquinazoline-l-yl, 5- Chloro-7—fluoroquinazoline-1-yl, 6—Chloro-7—Fluoroquinazoline-1-yl, 7—Chloro-5—Fluoroquinazoline-1-yl, 7—Chloro-1 6-Fluoroquinazoline 1-2-yl, 7-Black mouth 6-Cyanokinazoline 1-2-yl, 7-Ciano 6-Fluoroquinazoline 1-2-yl, 6-Fluoro 7-trifluoro A tricyclic compound selected from the group consisting of romethylquinazoline-1-yl and 5,6,7-trifluoroquinazoline-2-yl groups;

(17). In the compound represented by the formula (I), A is 2_thiazolyl, 1,3,4-thiadiazol-12-yl, 2-pyridyl, 2-pyrimidinyl, 2-benzoxazolyl, 2-Venzothiazolyl, quinolin-1-yl, quinazoline-1-yl, 4-methyl_2-thiazolyl, 4-isopropyl-12-thiazolyl, 4-t-butyl-1-2-thiazolyl, 4-trifluoromethylol 2-thiazolyl, 5-methyl-1,3,4-thiadiazol-2-yl, 5-isopropyl-1,3-, 3-thiadiazol-2-yl, 5-tert-butyl-1,3,4— Thiadiazol-2-yl, 5-trifluoromethyl-1,3,4-thiadiazol-2-yl, 5,6-difluoro-2-pyridyl, 5, 6-dichloro-1-pyridyl, 5,, 6-dimethyl-2-pyridyl, 5, 6-dihydrocyclopen [B] Pyridine-2-yl, 5,6,7,8-tetrahydroquinoline-12-yl, 5,6-difluoro-2-pyrimidinyl, 5,6-dichloro-1--2-pyrimidinyl, 6_Dimethyl-2-pyrimigel, 6_Trifluoromethyl-2-pyrimidinyl, 5,6-dihydrocyclopentene [d] pyrimidin-2-yl, 5,6,7,8-tetrahydroquinazoline-1-yl , 6 —Fluoro-2-benzobenzozolyl, 5 —Fluoro-2-benzoxazolyl, 5, 6 —Difluoro-2-benzobenzozolyl, 6 _ 2-Benzoxazolyl, 5-Chloro-2-benzobenzozolyl, 5,6-dichloro-2-benzobenzozolyl, 5-Chloro-1-6-fluoro-2-benzobenzoxazolyl, 5-Methyl-1-2 —Benzoxazolyl, 5 —Cyano-2-benzoxazolyl, 5 —Trifluoromethyl-2-benzobenzozolyl, 5 —Methylthio-1-benzobenzoxazolyl, 6 —Fluoro-2-benzothiazolyl, 5 —Fluoro-2-benzothiazolyl, 5,6-difluoro-2 —benzothiazolyl, 6 —chloro-2 benzothiazolyl, 5-chloro_2 —benzothiazolyl, 5, 6 —dichloro1-2 —benzothiazolyl, 5-chloro 6-Fluoro-2-benzothiazolyl, 5-methyl-2-benzothiazolyl, 5-cyano-2-benzothiazolyl, 5-trifluoromethyl-2-ben Zothiazolyl, 5-methylthio-1-benzothiazolyl, 5-fluoroquinoline 1-2-yl, 6-fluoroquinoline 1-2-yl, 7-fluoroquinoline 1-2-yl, 5-chloroquinoline 1-2-yl, 6-Chloroquinoline-1-yl, 7-Chloroquinolin-2-yl, 7-Methylquinoline-2-yl, 7-Trifluoromethylquinoline 1-2-yl, 7-Methoxyquinoline_2 —Yl, 7—difluorome toxic quinoline 1-2 — yl, 7—trifluoromethyl quinoline _ 2 — yl, 5,7—difluoroquinoline 1-2—yl, 6, 7—difluoroquinoline 1 2 —Yl, 5,7—dichloroquinoline 1-2 yl, 6,7—dichloroquinoline 1-2 —yl, 5—black mouth _ 7—fluoroquinoline 1-2 —yl, 6—black mouth 7—fluoroquinoline One 2 _ ill, 7 — Black mouth 1 _ Fluoro Norin one 2 - I Lumpur, 7-chloro

6-Fluoroquinoline 1-2 _yl, 7-Black mouth 6-Cyanoquinoline 1-2-yl, 7-Cyano 6-Fluoroquinoline 1-2-yl, 6-Fluoro-7—Trifluoromethylquinoline 1-2 5-, 6-, 7-Trifluoroquinoline 2- 2-, 5- 5-Fluoroquinazoline 2--yl, 6- Fluoroquinazoline_2--yl, 7- Fluoroquinazoline 2 — yl, 5 — black quinazoline 1 2 — yl, 6 — black quinazolin 1 2 — yl, 7 — black quinazoline 1 2 — yl, 7—methylquinazoline 1 2 — yl , 7 _ trifluoromethylquinazoline _ 2-yl,

7-Methoxyquinazoline 1-2-yl, 7-Difluorome toxic quinazoline 1-2-yl, 7-Trifluorome toxic quinazoline 1-2-yl, 5, 7-Difluoroquinazoline 1-2-yl,

6,7-Difluoroquinazolin-l-yl, 5,7-Dichloroquinazolin-l-yl, 6,7-Dichloroquinazoline-l- 2-yl, 5-Chloro-7-fluoroquinazoline_ 2 — yl, 6 — black mouth 7 _ fluoroquinazoline 1 2 — yl, 7 — black mouth 1 5 — fluoroquinazoline 1 — 2-yl, 7 — black mouth 6 — fluoroquinazoline 2-I-yl, 7-chloro-6-cyanoquinazolin-2-yl, 7-cyano 6 _fluoroquinazoline 1-2-yl, 6-fluoro-7-trifluoromethylquinazoline 1-2-yl and A tricyclic compound selected from the group consisting of 5, 6, 7_ trifluoroquinazoline-12-yl group,

(18). In the compound represented by the formula (I), A is 2-pyridyl, 2-benzothiazolyl, quinoline-1-yl, 5,6-difluoro-2-pyridyl, 5,6-dichloro-1 —Pyridyl, 5, 6-dimethyl-1-pyridyl, 5,6,7,8 —tetrahydroquinolin-12-yl, 6-fluoro-2-benzothiazolyl, 5-fluoro-2-benzothiazolyl, 5,6-diflur Ollow 2 benzothiazolyl, 6-chloro-2-benzothiazolyl, 5-chloro-2-benzothiazolyl, 5,6-dichloro-12-benzothiazolyl, 5-chloro-1 6-fluoro-2-benzothiazolyl, 5-methyl-1 2 —Benzothiazolyl, 5-cyano-2-benzothiazolyl, 5-trifluoromethyl-12-benzothiazolyl, 5-methylthio_2_benzothiazolyl, 5-fluoroquinoline-12-yl, 6-fluoroquinoline-12-yl 7-Fluoroquinoline 1-2-yl, 5-Black quinoline 1-2-yl, 6-Black quinoline 1-2-yl, 7-Chloroquinoline 1-2-yl, 7-Methylquinoline 1-2 —Yl, 7—Trifluoromethylquinoline 1-2 yl, 7—Methoxyquinoline 1-2 yl, 7—Difluoromethoxyquinoline 1-2 yl, 7—Trifluoromethyl quinoline Quinoline 1-2-yl, 5,7-Difluoroquinoline 1-2-yl, 6, 7-Difluoroquinoline 1-2-yl, 5, 7-Dichloroquinoline 1-2-yl, 6, 7 —Dichloroquinoline 1-2-yl, 5-chloro-1- 7-Fluoroquinoline 2-yl, 6-chloro 7-Fluoroquinoline 1-2-yl, 7-Chromo-1-5-fluoroquinoline 1-2-yl 7-chloro-6-cyanoquinoline 1-2-yl, 7-cyano-6-fluoroquinoline 1-2-yl, 6-fluoro-7-trifluoroquinoline quinoline 1-2 A tricyclic compound selected from the group consisting of yl and 5,6,7-trifluoroquinoline-12-yl groups;

(1 9). A of the compound represented by the formula (I) is 7-fluoroquinoline-1-yl, 7-chloroquinoline_2-yl, 6,7-difluoroquinoline-12-yl 6,7-dichloroquinolin-2-yl, 7-chloro-6-fluoroquinoline-2-yl, 6-fluoro-7-trifluoromethylquinoline-1-yl and 5,6,7,8- A tricyclic compound selected from the group consisting of tetrahydroquinoline-l-2-yl group,

(20). A tricyclic compound in which B in the formula (I) is a formula of OCH ₂ —, a formula — CH ₂₀ — or a formula —CH ₂ CH ₂ —,

(21) a tricyclic compound in which X in the formula (I) is a methylene group, a sulfur atom or an oxygen atom,

(22). In the formula (I), Y is methylene, ethylene, trimethylene, tetramethylene, pentamethylene, fluoromethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2 , 2-Difluoroethylene, 1-methylethylene, 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene, 1-methoxyethylene, 2-methoxy Ethylene, 1-fluorotrimethylene, 2_fluorotrimethylene, 3_fluorotrimethylene, 1,1difluorotrimethylene, 2,2-difluorotrimethylene, 3,3-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1 , 1-dimethyltrimethylene, 2,2-dimethyltrimethyl Ren, 3, 3-dimethyl trimethylene, 2, 2-Jechiru Trimethylene, 2-methoxy trimethylene, 3-methoxy trimethylene, 2,2-dimethyl trimethylene, 3,3-dimethyl trimethylene, 1,2-phenylene, 1,3-phenylene group, In the group represented by the formula (a), a group where o = 0, p = 0, q = l, a group where o = 0, p = 1, q = l, o = 0, p = 1, q = Group 2, 0 = 1, p = 0, q = l, o = l, p = 1, q = 1, and 0 = 1, p = 1, q = 2 A tricyclic compound selected from the group consisting of:

(23). Y-methylene, ethylene, trimethylene, fluoromethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, and 1-methyl in the formula (I). Ethylene, 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene, 1-fluorotrimethylene, 2-fluorotrimethylene, 3-fluorotrimethylene 1,1, difluorotrimethylene, 2,2-difluorotrimethylene, 3,3-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene Methylene, 3,3-dimethyltrimethylene, 1,2-phenylene, and groups represented by formula (a) From the group consisting of groups with o = l, p = 0, q = l, groups with o = l, p = 1, q = 1, and groups with 0 = 1, p = l, q = 2 A selected tricyclic compound, (24). In the formula (I), Y is methylene, ethylene, trimethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2 , 2-Difluoroethylene, 1-methylethylene, 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene, 2,2-difluorotrimethylene, 1- For methyltrimethylene, 2-methyltrimethylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, 1,2-phenylene and the group represented by the formula (a) , O = l, p = 1, q = l Tricyclic compounds are those selected from the group consisting of,

(25). In the formula (I), Y is methylene, ethylene, trimethylene, 1-methylethylene, 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene. , 1,2-phenylene and a tricyclic compound selected from the group consisting of a group represented by the formula (a), wherein o = l, p = 1, q = 1,

(26). Formula (I) Z force ⁵ 'in, carboxy, 1 H- tetrazole one 5- I le, wherein one S0 ₃ H, methanesulfonyl § amino, ethanesulfonyl § Mino, triflumizole Ruo b methanesulfonyl amino, off Enylsulfonylamino, p-fluorophenylsulfonylamino, p-chlorophenylsulfonylamino, 0-methylphenylsulfonylamino, p-methylphenylsulfonyl Amino, p-Trifluoromethylphenylsulfonylamino, 0-Methoxyphenylsulfonylamino, p-Methoxyphenylsulfonylamino, p-Difluoromethoxyphenylsulfonylamino, p-Trifluoromethylsulfonylamino, p-Trifluoromethylsulfonylamino Amino, p-nitrophenylsulfonylamino, p-cyanophenylsulfonylamino, methanesulfonylaminocarbonyl, ethanesulfonylaminocarbonyl, trifluoromethanesulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, p-fluoro Phenylsulfonylaminocarbonyl, p-methylphenylsulfonylaminocarbonyl, 0-methylphenylsulfonylaminocarbonyl, p-methylphenylsulfonylaminocarbonyl, p-trifluoromethylphenyl Rusulfonylaminocarbonyl, 0-Methoxyphenylsulfonylaminocarbonyl, p-Methoxyphenylsulfonylaminocarbonyl, p-Difluoromethoxyphenylsulfonylamino Power Luponyl, p-Trifluoromethoxyphenylsulfonylaminocarbonyl A tricyclic compound selected from the group consisting of p-ditrophenylsulfonylaminocarbonyl and p-cyanophenylsulfonylaminocarbonyl, (27). In the formula (I), Z is carboxy, 1 H- tetrazole one rule 5_ I le, wherein one S0 ₃ H, methanesulfonyl § Mino, triflumizole Ruo b methanesulfonyl § Mino, phenylalanine sulfonyl § amino, O-methyl phenylalanine sulfonyl § amino, p- methyl phenylalanine sulfonyl Amino, methane sulfonylaminocarbonyl, trif A tricyclic compound selected from the group consisting of fluoromethanesulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, 0-methylphenylsulfonylaminocarbonyl and p-methylphenylsulfonylaminocarbonyl group,

(28) Z in. Formula (I) are, carboxy, wherein one S0 ₃ H, methanesulfonyl § Mino, triflumizole Ruo b methanesulfonyl § Mino, from the group consisting of methanesulfonyl § amino carbonyl and Torifuruo port methanesulfonyl § amino group A tricyclic compound that is selected,

(29). A tricyclic compound in which m in the formula (I) is an integer of 1, 2, or 3.

(30). A tricyclic compound in which n in the formula (I) is an integer of 1 or 2.

For R ', the preferred ranking increases in the order of (1) to (5), for R ^{2 the} preferred ranking increases in the order of (6) to (8), and for A, (9) From (12), from (13) to (16) and from (17) to (20), the preferred ranking increases. For Y, the preferred ranking increases from (23) to (26), and for Z Is preferred in the order of (27) to (29).

Further, as the tricyclic compound having the general formula (I), a tricyclic compound comprising a combination of two or more of the above (1) to (30) is also preferable. Specific preferred examples of the compound (I) include the compounds shown in Table 1 below. Can be <

 Table 1

o. A B (R²)n (R')m X-Y-Z

o. AB (R ² ) n (R ') m XYZ

1 6,7-diF-Q -OCH ₂ -HH-OGH ₂ COOH

2 6,7-diF-Q-OCH ₂ -HH -OCH ₂ CH ₂ COOH

3 6,7-diF-Q-OCH ₂ -HH -OCH ₂ CH (CH ₃ ) COOH

6,7-diF-Q -OCH ₂ -HH -OCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

5 6,7-diF-Q -OCH ₂ -HH -SCH ₂ COOH

6 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CH ₂ COOH

7 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

8 6,7-diF-Q -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

9 6,7-diF-Q -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) COOH0 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CH (CH ₂ CH ₃ ) COOH 1 6, 7-diF-Q-OGH ₂ -HH -SCH (CH ₃ ) CH ₂ COOH

2 6,7-diF-Q-OGH ₂ -HH-SC (CH ₃ ) ₂ CH ₂ COOH

3 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) CH ₂ COOH4 6,7-diF-Q-OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH5 6 , 7-diF-Q -OCH ₂ -HH -SCH ₂ C (CH ₂ ) CCOOH

6 6,7-diF-Q -OCH ₂ -HH-S (2-COOH-Ph)

7 6,7-diF-Q -OCH ₂ -HH-S (3-COOH-Ph)

8 6,7-diF-Q -OCH ₂ -HH-S (4-COOH-Ph)

9 6,7-diF-Q -OCH ₂ -HH-SCH ₂ -Tet

0 6,7-diF-Q -OCH ₂ -HH ^_ SCH ₂ CH ₂ ~ 1 et

1 6,7-diF-Q -OCH ₂ -HH -SCH ₂ NHS0 ₂ CF ₃

2 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CONHS0 ₂ CH ₃

3 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CONHS0 ₂ CF ₃

4 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CONHS0 ₂ Ph

5 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CONHS0 ₂ (2-CH ₃ -Ph) 6 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CH ₂ NHS0 ₂ CF ₃

7 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CH ₂ CONHS0 ₂ CH ₃ 8 6,7-diF-Q-OCH ₂ -HH -SCH ₂ CH ₂ CONHS0 ₂ CF ₃ 9 6,7-diF _{-Q -OCH 2 - HH -SCH 2 CH} 2 CONHS0 2 Ph0 6,7-diF-Q -OCH 2 - HH -SCH 2 CH 2 CONHS0 2 (2-CH 3 -Ph) 1 6,7-diF-Q -OCH ₂ -HH -SCH ₂ CH ₂ S0 ₃ H

2 6,7-diF-Q-OGH ₂ -HH -CH ₂ CH ₂ CH ₂ COOH

3 6,7-diF-Q -OCH ₂ -HH = CHCH ₂ CH ₂ COOH

4 6,7-diF-Q -OCH ₂ -HH = CHCH = CHCOOH 6,7-diF-Q -OCH ₂ -H 7-F -SCH ₂ COOH

6J-diF-Q-OCH ₂ -H 7-F -SCH ₂ CH ₂ COOH

6,7-diF-Q -OCH ₂ -H 7-F -SCH ₂ CH (CH ₃ ) COOH

6,7-diF-Q-OCH ₂ -H 7-F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

6,7-diF-Q -OCH ₂ -H 7-F -SCH ₂ C (CH ₃ ) ₂ COOH

6J-diF-Q -OCH ₂ -H 7-F -SC (CH ₃ ) ₂ CH ₂ COOH

6J- diF-Q-OGH ₂ -H 7-F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

6,7-diF-Q -OCH ₂ -H 7-F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

6,7-diF-Q -OCH ₂ -H 8-F -SCH ₂ COOH

6,7-diF-Q-OGH ₂ -H 8-F -SCH ₂ CH ₂ COOH

6,7-diF-Q-OGH ₂ -H 8-F -SCH ₂ CH (CH ₃ ) COOH

6,7-diF-Q -OCH ₂ -H 8-F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

6J-diF-Q -OCH ₂ -H 8-F -SCH ₂ C (CH ₃ ) ₂ COOH

6,7-diF-Q -OCH ₂ -H 8-F -SC (CH ₃ ) ₂ CH ₂ COOH

6J-diF-Q -OCH ₂ -H 8-F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

6J-diF-Q-OCH ₂ -H 8-F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

6J- diF-Q-OCH ₂ -H 9-F -SCH ₂ COOH

6,7-diF-Q-OCH ₂ -H 9-F -SCH ₂ CH ₂ COOH

6,7-diF-Q-OCH ₂ -H 9-F -SCH ₂ CH (CH ₃ ) COOH

6,7-diF-Q-OCH ₂ -H 9-F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

6,7-diF-Q -OCH ₂ -H 9-F -SCH ₂ C (CH ₃ ) ₂ COOH

6,7-diF-Q-OGH ₂ -H 9-F -SC (CH ₃ ) ₂ CH ₂ COOH

6,7-diF-Q-OCH ₂ -H 9-F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

6,7-diF-Q-OCH ₂ -H 9-F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

6,7-diF-Q -OCH ₂ -H 7-CN -SCH ₂ COOH

6,7-diF-Q -OCH ₂ -H 7-CN -SCH ₂ CH ₂ COOH

6J-diF-Q -OCH ₂ -H 7-CN -SCH ₂ CH (CH ₃ ) COOH

6,7-diF-Q -OCH ₂ -H 7-CN -SCH ₂ CH (CH ₂ CH ₃ ) COOH

6,7-diF-Q -OCH ₂ -H 7-CN -SCH ₂ C (CH ₃ ) ₂ COOH

6J-diF-Q -OCH ₂ -H 7-CN -SC (CH ₃ ) ₂ CH ₂ COOH

6,7-diF-Q -OCH ₂ -H 7-CN -SCH ₂ CH (CH ₃ ) CH ₂ COOH

6J-diF-Q -OCH ₂ -H 7-CN -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

6J-diF-Q -OGH ₂ -H 8-CN -SCH ₂ COOH

6,7-diF-Q -OCH ₂ -H 8-CN -SCH ₂ CH ₂ COOH

6,7-diF-Q -OCH ₂ -H 8-CN -SCH ₂ CH (CH ₃ ) COOH

6,7-diF- Q -OCH ₂ -H 8-CN -SCH ₂ CH (CH ₂ CH ₃ ) COOH

6,7-diF-Q-OCH ₂ -H 8-CN -SGH ₂ C (CH ₃ ) ₂ COOH

6,7-diF-Q-OGH ₂ -H 8-CN -SC (CH ₃ ) ₂ CH ₂ COOH

6,7-diF-Q -OCH ₂ -H 8-CN -SCH ₂ CH (CH ₃ ) CH ₂ COOH

6,7-diF-Q-OGH ₂ -H 8-CN -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

6,7-diF-Q-OCH ₂ -H. 9-CN -SCH ₂ COOH

6,7-diF-Q-OCH ₂ -H 9-CN -SCH ₂ CH ₂ COOH

6,7-diF-Q-OCH ₂ -H 9-CN -SCH ₂ CH (CH ₃ ) COOH

6,7-diF-Q -OCH ₂ -H 9-CN -SCH ₂ CH (CH ₂ CH ₃ ) COOH

6,7-diF-Q -OCH ₂ -H 9-CN -SCH ₂ C (CH ₃ ) ₂ COOH

6,7-diF-Q -OCH ₂ -H 9-CN -SC (CH ₃ ) ₂ CH ₂ COOH 81 6,7-diF-Q -OCH ₂ -H 9-CN -SCH ₂ CH (CH ₃ ) CH ₂ COOH

82 6,7-diF-Q -OCH ₂ -H 9-CN -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

83 6,7-diF-Q-OGH ₂ -H 7-CF ₃ -SCHjCOOH

84 6J-diF-Q-OGH ₂ -H -CF3 -SCH ₂ CH ₂ COOH

85 6,7-diF-Q -OCH ₂ -H 7-CF3 -SCH ₂ CH (CH ₃ ) COOH

86 6,7— diF-Q -OCH ₂ -H -CF3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

87 6,7-diF-Q -OCH ₂ -H 7-CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

88 6,7— diF-Q -OCH ₂ -H -CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

89 6J- diF-Q-OGH ₂ -H 7-CF3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

90 6,7-diF-Q -OCH ₂ -H -CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

91 6,7-diF-Q -OCH ₂ -H 8-CF3 -SCH ₂ COOH

92 6,7-diF-Q-OGH ₂ -H 8-CF3 -SCH ₂ CH ₂ COOH

93 6,7-diF-Q-OGH ₂ -H 8-CF3- -SCH ₂ CH (CH ₃ ) COOH

94 6,7-diF-Q -OCH ₂ -H 8-CF3- -SCH ₂ CH (CH ₂ CH ₃ ) COOH

95 6,7-diF-Q -OCH ₂ -H 8-CF3-SCH ₂ C (CH ₃ ) ₂ COOH

96 6,7-diF-Q -OCH ₂ -H 8-CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

97 6,7-diF-Q-OGH ₂ -H 8-CF3- -SCH ₂ CH (CH ₃ ) CH ₂ COOH

98 6,7-diF-Q -OCH ₂ -H 8-CF3- -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

99 6,7-diF-Q -OCH ₂ -H 9-CF3 -SCH ₂ COOH

100 6,7-diF-Q -OCH ₂ -H 9-CF3 -SCH ₂ CH ₂ COOH

101 6,7-diF-Q -OCH ₂ -H 9-CF3 -SCH ₂ CH (CH ₃ ) COOH

102 6,7-diF-Q -OCH ₂ -H 9-CF3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

103 6,7-diF-Q -OCH ₂ -H 9-CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

104 6J-diF-Q -OCH ₂ -H 9-CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

105 6,7-diF-Q -OCH ₂ -H 9-CF3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

106 6J-diF-Q -OCH ₂ -H 9-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

107 6,7-diF-Q -OCH ₂ -H 7-G3 GH -SCH ₂ COOH

108 6,7-diF-Q -OCH ₂ -H 7-C≡CH -SCH ₂ CH ₂ COOH

109 6J-diF-Q -OCH ₂ -H 7 -G3 GH -SCH ₂ CH (CH ₃ ) COOH

1 10 6,7-diF-Q -OCH ₂ -H 7-G3 GH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

1 1 1 6,7-diF-Q -OCH ₂ -H 7-C≡CH -SCH ₂ C (CH ₃ ) ₂ COOH

1 12 6,7-diF-Q -OCH ₂ -H 7-C = CH -SC (CH ₃ ) ₂ CH ₂ COOH

1 13 6J-diF-Q-OCH ₂ -H 7-C3 GH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

1 14 6,7-diF-Q -OCH ₂ -H 7-C3 CH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

1 15 6,7-diF-Q -OCH ₂ -H 8-C = CH -SCH ₂ COOH

1 16 6,7-diF-Q -OCH ₂ -H 8-C3 CH -SCH ₂ CH ₂ COOH

1 1 7 6,7-diF-Q -OCH ₂ -H 8_C3 CH -SCH ₂ CH (CH ₃ ) COOH

1 18 6,7-diF-Q -OCH ₂ -H 8 -C3 CH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

1 19 6,7-diF-Q -OCH ₂ -H 8 -C3 CH -SCH ₂ C (CH ₃ ) ₂ COOH

120 6J-diF-Q -OCH ₂ -H 8 -C3 CH -SC (CH ₃ ) ₂ CH ₂ COOH

121 6J-diF-Q -OCH ₂ -H 8 -G3 GH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

122 6,7-diF-Q -OCH ₂ -H 8-C = CH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

123 6,7-diF-Q -OCH ₂ -H 9-C = CH -SCH ₂ COOH

124 6,7-diF-Q -OCH ₂ -H 9-C≡CH -SCH ₂ CH ₂ COOH

125 6J-diF- Q-OCH ₂ -H 9-C3 CH -SCH ₂ CH (CH ₃ ) COOH

一 ϋし H₂ - 9-G三 GH 一 oし Gh₃)₂し H₂し ϋϋΗ126 6,7-diF-Q -OCH ₂ -H 9-C3 CH-SCH ₂ CH (CH ₂ CH ₃ ) COOH 1 and / ααι ^ u One U ₂ M 9 Π 9-C≡CH ₂ H ₂

One ϋ and H ₂ - 9-G three GH one o and Gh _{3) 2} Mr. H ₂ Mr. ϋϋΗ

Ί D, / ail ■ UU then M ₂ _ 9-C≡CH H ₂ Η (y y Η ₂ DUH

0, / all ^ Re U n ₂ 9-C = CH ti h h ₂ M M ₂ U UUI

131 6, / -ail "1 U 1 ₂ 7-C (CH ₃ ;) ₂ 0H -SCH ₂ C00H

1 b _f / -ail U U π 7-C (CH ₃ :) ₂ 0H

1 D _r / all ■ U ϋ

And _{Μ 2 - Π 7-C (} CH 3:) 2 0H oneヽ

Then i ₂ then Ht ^ U y then (J (JH

I o4 0, / all ^ U one ϋ and _{Η 2 - 7-C (CH} 3:) 2 0H one t> to Eta ₂ Mr. Eta and H ₂ teeth (JOH

1 Jo / -all ~ U one U H ₂ — Η 7-C (CH ₃ :) ₂ 0H one H ₂ shit H ₃ ) ₂ GO (JH

1 0, / all ^ one U¾ and * w π.- Π 7-C ( CH 3:) 2 0H by ^ teeth Μ ₃ Mr. fi ₂ Mr.

1 / o, / ail ^ u Π 7-C (GH ₃ :) ₂ 0H then 1 ₂ then i then M ₃ then H ₂ then UUI

1 D, / ai u-r u 7-C (CH ₃ :) ₂ 0H then M ₂ then M ₂ then I 2 then M ₂ UUM a 0, / air Π 8-C (GH ₃ :) ₂ 0H

o, / air u Π 8-C (CH ₃ :) ₂ 0H then π ₂ then uun

1 ½ 1 \ D, / all ^ u π 8- C (CH 3:) 2 0H and M ₂ Mr. [pi, and t ₃ Mr. UUH

1 0, / air U then 8-C (CH ₃ :) ₂ 0H, then ri, Shi, Liun 1 o, / ai w — Π Ι-Ι ― 8-C (CH ₃ :) ₂ 0H p ^ pu, pnnw

1 / all "U Π 8- C (CH 3:) 2 0H one b lion Η _{3 (ί 2} Mr. H ₂ Mr. ϋϋΗ

14 o, / ail ^ j one u ―

Li and _{M 2 Π 8-C (CH} 3:) 2 0H and li ₂ Mr. h and H ₃ Mr. l ^ to UUH

1 0 0, / dil ^ U and Π, Π 8-C (CH 3:) 2 0H and M ₂ and Shi Ms and M ₂ Mr. M ₂ Mr. UUM

14 / -ail "one UU and Μ - Π 9-C (CH 3:) 2 0H one Mr. H ₂ Mr. UUH

 148 6 ":"

^{_{, -DiF-Q -OCH 2 _ π}} 9-C (CH 3:) 2 0H one SGH ₂ GH ₂ GOOH

1 9 b, / one m ': l "- U one ϋ and _{H 2 - π 9-C (} CH 3:) 2 0H one SGH ₂ Gh and H ₃₎ Ji ΟϋΗ b, / -ail" one U one U and _{H 2 - π 9- C (GH} 3:) 2 0H one b and Eta ₂ and Shi Eta ₂ Mr. _Η 3ί) to CJU i

101 D, / all ~ U UUn 2 9-C (CH 3:) 2 0H - b and H ₂ lion H ₃ Mr. (JCJ l 0 0, -nw- 9 -C (CH 3:) Shi and ₂ 0Hリ

1 0, air w Π 9-C (CH ₃ :) ₂ 0H ί ri ri U U U U (Jn

1 o, / air ίοί Π 9- C (CH ₃ :) ₂ 0H ¾ n ₂ , n ₂ , n ₂ノ uun

I 00 O r, / p then | one π re Π Π H ¾ _{2 2} M ₂ Li LiUM

 00 | _n — no and w. ―One H

10 / O r, / l U Li and M ₂ H and Micromax ₂ lion H ₃ J ₂ Mr. UUI

1 Oo 0, / 1 1 U — M M ₂ u u π H b M M ₂ H H ₂ 2 2 し UUM

1 1! Dy Or, / 1 1 π 7-F M M ₂ M M ₂ U UUi

 1 n

 0 r, / l j — now― | _ | 7-F し し Π, し ノ し り (Jn

ID / 1 1 U —now ― Π 7-FM ₂に し M ₃

 / 1 1 7-F-、 し ri ri un un

Or, π 8-F then π, then π ₂ υπ fi_p 7-pn .Η 一 Π 8-F-<M, r * nnw

1 fi— 7-pl-O -ΠΡ.Η 一 u 8-F _opu, ΠΗ ΠΗ I OO -Π Η * Η rig Π 8-F ^^ ⁷门 リ n Π 9-F 0 リun

1 り — 卜, “/ 7— し 1— OUU then M ₂ Π 9-F i then l ₂ then ^ f ₃ then UU l

169 6-F.7-CI-Q -0CH ₂ -Η 9-F-SGH ₂ 〇 (CH ₃ ) ₂ COOH

170 6- F, 7-0 (3-0GH ₂ -Η 9-F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

171 7-FQ-0〇H ₂ -Η H. -SCH ₂ CH ₂ COOH

172 7-FQ-0GH ₂ -Η H -SCH ₂ CH (CH ₃ ) COOH 1 73 7-FQ-OGH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

1 74 7-FQ-OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

1 75 7-FQ -OCH ₂ -H 7-F -SCH ₂ CH ₂ COOH

176 7-FQ-OCH ₂ -H 7-F -SCH ₂ CH (CH ₃ ) COOH

177 7-FQ-OGH ₂ -H 7-F -SCH ₂ C (CH ₃ ) ₂ COOH

1 78 7-FQ -OCH ₂ -H 7-F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

1 79 7-FQ -OCH ₂ -H 8-F -SCH ₂ CH ₂ COOH

180 7-FQ -OCH ₂ -H 8-F -SCH ₂ CH (CH ₃ ) COOH

181 7-FQ-OCH ₂ -H 8-F -SCH ₂ C (CH ₃ ) ₂ COOH

182 7-FQ-OCH ₂ -H 8-F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

183 7-FQ -OCH ₂ -H 9-F -SCH ₂ CH ₂ COOH

184 7-FQ -OCH ₂ -H 9-F -SCH ₂ CH (CH ₃ ) COOH

185 7-FQ -OCH ₂ -H 9-F -SCH ₂ C (CH ₃ ) ₂ COOH

186 7-FQ -OCH ₂ -H 9-F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

1 87 7-FQ -OCH ₂ -H 7-C≡GH -SCH ₂ CH ₂ COOH

188 7-FQ -OCH ₂ -H 7-C≡CH -SCH ₂ CH (CH ₃ ) COOH

1 89 7-FQ-OGH ₂ -H 7-C3 GH -SCH ₂ C (CH ₃ ) ₂ COOH

190 7-FQ -OCH ₂ -H 7-C≡CH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

191 7-FQ -OCH ₂ -H 8-C≡CH -SCH ₂ CH ₂ COOH

192 7-FQ -OCH ₂ -H 8-C≡CH -SCH ₂ CH (CH ₃ ) COOH

193 7-FQ-OGH ₂ -H 8-C≡CH -SCH ₂ C (CH ₃ ) ₂ COOH

194 7-FQ -OCH ₂ -H 8-C≡GH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

195 7-FQ -OCH ₂ -H 9-C≡GH-SCH ₂ CH ₂ COOH

196 7-FQ -OCH ₂ -H 9-G3 GH -SCH ₂ CH (CH ₃ ) COOH

197 7-FQ -OCH ₂ -H 9-G = CH -SCH ₂ C (CH ₃ ) ₂ COOH

198 7-FQ-OCH ₂ -H 9-C≡CH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

199 7-FQ -OCH ₂ -H 7-CF ₃ -SCH ₂ CH ₂ COOH

200 7-FQ -OCH ₂ -H -CF3 -SCH ₂ CH (CH ₃ ) COOH

201 7-FQ -OCH ₂ -H 7-CF3-SGH ₂ C (CH ₃ ) ₂ COOH

202 7-FQ-OGH ₂ -H 7-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

203 7-FQ -OCH ₂ -H 8-CF3 -SCH ₂ CH ₂ COOH

204 7-FQ-OGH ₂ -H 8-CF3 -SCH ₂ CH (CH ₃ ) COOH

205 7-FQ-OCH ₂ -H 8-CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

206 7-FQ -OCH ₂ -H 8-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

207 7-FQ-OCH ₂ -H 9-CF3 -SCH ₂ CH ₂ COOH

208 7-FQ -OCH ₂ -H 9-CF3 -SCH ₂ CH (CH ₃ ) COOH

209 7-FQ -OCH ₂ -H 9-CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

210 7-FQ-OGH ₂ -H 9-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

21 1 7-FQ-OCH ₂ -H 7-C (CH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

212 7-FQ -OCH ₂ -H 7-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH

213 7-FQ-OGH ₂ -H 7-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

214 7-FQ -OCH ₂ -H 7 -C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

215 7-FQ -OCH ₂ -H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

216 7-FQ -OCH ₂ -H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH

21 7 7-FQ -OCH ₂ -H 8 -C (GH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

218 7-FQ -OCH ₂ -H 8-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH 219 7-FQ -OCH ₂ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

220 7-FQ-OCH ₂ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH

221 7-FQ -OCH ₂ -H 9-C (CH ₃ ) ₂ OH-SCH ₂ C (CH ₃ ) ₂ COOH

222 7-FQ-OCH ₂ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

223 7-CI-Q-OGH ₂ -HH -SCH ₂ COOH

224 7-CI-Q-OGH ₂ -HH -SCH ₂ CH ₂ COOH

225 7-CI-Q-OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

226 7-CI-Q -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

227 7-CI-Q-OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

228 TQ -OCH ₂ -HH -SCH ₂ COOH

229 TQ -OCH ₂ -HH-SCH ₂ CH ₂ COOH

230 TQ -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

231 TQ-OCH ₂ -HH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

232 TQ -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

233 TQ -OCH ₂ -HH -SC (CH ₃ ) ₂ CH ₂ COOH

234 TQ -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

235 TQ -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

236 TQ -OCH ₂ -H 7-F -SCH ₂ COOH

237 TQ -OCH ₂ -H 7-F -SCH ₂ CH ₂ COOH

238 TQ-OCH ₂ -H 7-F -SCH ₂ CH (CH ₃ ) COOH

239 TQ-OCH ₂ -H 7-F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

240 TQ-OGH ₂ -H 7-F -SCH ₂ C (CH ₃ ) ₂ COOH

241 TQ -OCH ₂ -H 7-F -SC (CH ₃ ) ₂ CH ₂ COOH

242 TQ -OCH ₂ -H 7-F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

243 TQ -OCH ₂ -H 7-F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

244 TQ-OCH ₂ -H 8-F -SCH ₂ COOH

245 TQ -OCH ₂ -H 8-F -SCH ₂ CH ₂ COOH

246 TQ -OCH ₂ -H 8-F -SCH ₂ CH (CH ₃ ) COOH

247 TQ-OCH ₂ -H 8-F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

248 TQ -OCH ₂ -H 8-F-SCH ₂ C (CH ₃ ) ₂ COOH

249 TQ -OCH ₂ -H 8-F -SC (CH ₃ ) ₂ CH ₂ COOH

250 TQ-OGH ₂ -H 8-F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

251 TQ-OCH ₂ -H 8-F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

252 TQ -OCH ₂ -H 9-F -SCH ₂ COOH

253 TQ -OCH ₂ -H 9-F -SCH ₂ CH ₂ COOH

254 TQ -OCH ₂ -H 9-F -SCH ₂ CH (CH ₃ ) COOH

255 TQ-OCH ₂ -H 9-F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

256 TQ-OGH ₂ -H 9-F -SCH ₂ C (CH ₃ ) ₂ COOH

257 TQ -OCH ₂ -H 9-F -SC (CH ₃ ) ₂ CH ₂ COOH

258 TQ -OCH ₂ -H 9-F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

259 TQ -OCH ₂ -H 9-F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

260 TQ -OCH ₂ -H 7-C = CH -SCH ₂ COOH

261 TQ -OCH ₂ -H 7-C ≡CH -SCH ₂ CH ₂ COOH

262 TQ -OCH ₂ -H 7-C ≡CH -SCH ₂ CH (CH ₃ ) COOH

263 TQ -OCH ₂ -H 7-C ≡CH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

264 TQ -OCH ₂ -H 7-C = CH -SCH ₂ C (CH ₃ ) ₂ COOH 265 TQ -OCH ₂ -H 7- C3 GH -SC (CH ₃ ) ₂ CH ₂ COOH

266 TQ -OCH ₂ -H 7 -C3 CH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

267 TQ -OCH ₂ -H 7- C3 CH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

268 TQ -OCH ₂ -H 8- C≡CH -SCH ₂ COOH

269 TQ -OCH ₂ -H 8-C3 CH -SCH ₂ CH ₂ COOH

270 TQ -OCH ₂ -H 8-G3 CH -SCH ₂ CH (CH ₃ ) COOH 271 TQ -OCH ₂ -H 8-G3 CH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

272 TQ -OCH ₂ -H 8-G 3 CH -SCH ₂ C (CH ₃ ) ₂ COOH

273 TQ -OCH ₂ -H 8-G3 GH -SC (CH ₃ ) ₂ CH ₂ COOH

274 TQ -OCH ₂ -H 8-C3 CH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

275 TQ -OCH ₂ -H 8- C = CH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

276 TQ OCH ₂ -H 9- C≡CH -SCH ₂ COOH

277 TQ -OCH ₂ -H 9-C3 CH -SCH ₂ CH ₂ COOH

278 TQ -OCH ₂ -H 9-G 3 CH -SCH ₂ CH (CH ₃ ) COOH

279 TQ -OCH ₂ -H 9-C = CH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

280 TQ -OCH ₂ -H 9 -G 3 GH -SCH ₂ C (CH ₃ ) ₂ COOH 281 TQ -OCH ₂ -H 9 -C 3 CH -SC (CH ₃ ) ₂ CH ₂ COOH

282 TQ -OCH ₂ -H 9-C3 GH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

283 TQ -OCH ₂ -H 9-C 3 CH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

284 TQ -OCH ₂ -H 7-CF ₃ -SCH ₂ COOH

285 TQ -OCH ₂ -H -CF3 -SCH ₂ CH ₂ COOH

286 TQ -OCH ₂ -H 7-CF3 -SCH ₂ CH (CH ₃ ) COOH

287 TQ -OCH ₂ -H 7-CF, -SCH ₂ CH (CH ₂ CH ₃ ) COOH

288 TQ -OCH ₂ -H 7-CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

289 TQ -OCH ₂ -H -CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

290 TQ -OCH ₂ -H -CF3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH 291 TQ -OGH ₂ -H-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

292 TQ -OCH ₂ -H 8- CF3 -SCH ₂ COOH

293 TQ -OCH ₂ -H 8-CF3 -SCH ₂ CH ₂ COOH

294 TQ -OCH ₂ -H 8-CF3 -SCH ₂ CH (CH ₃ ) COOH

295 TQ -OCH ₂ -H 8-CF3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

296 TQ -OCH ₂ -H 8-CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

297 TQ -OCH ₂ -H 8-CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

298 TQ -OCH ₂ -H 8-CF3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

299 TQ -OCH ₂ -H 8- CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

300 TQ -OCH ₂ -H 9- CF3 -SCH ₂ COOH

301 TQ -OCH ₂ -H 9-CF3 -SCH ₂ CH ₂ COOH

302 TQ -OCH ₂ -H 9-CF3 -SCH ₂ CH (CH ₃ ) COOH

303 TQ -OCH ₂ -H 9-CF3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

304 TQ -OCH ₂ -H 9-CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

305 TQ -OCH ₂ -H 9-CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

306 TQ -OCH ₂ -H 9-CF ₃ -SCH ₂ CH (CH ₃ ) CH ₂ COOH

307 TQ -OCH ₂ -H 9-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

308 TQ -OCH ₂ -H 7-C (CH ₃ ) ₂ OH -SCH ₂ COOH

309 TQ -OGH ₂ -H 7-C (GH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

310 TQ -OGH Factory H 7-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH 31 1 TQ _OGH ₂ -H 7-C (GH ₃ ) ₂ OH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

312 TQ-OCH ₂ -H 7-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

313 TQ-OCH ₂ -H 7-C (CH ₃ ) ₂ OH -SC (CH ₃ ) ₂ CH ₂ COOH

314 TQ -OCH ₂ -H 7-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

315 TQ -OCH ₂ -H 7-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

316 TQ -OCH ₂ -H 8-C (CH ₃ ) ₂ OH -SCH ₂ COOH

31 7 TQ-OCH ₂ -H 8-G (CH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

318 TQ-OGH ₂ -H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH

319 TQ -OCH ₂ -H 8-G (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

320 TQ-OCH ₂ -H 8-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

321 TQ -OCH ₂ -H 8-C (CH ₃ ) ₂ OH -SC (CH ₃ ) ₂ CH ₂ COOH

322 TQ -OCH ₂ -H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

323 TQ -OCH ₂ -H 8 -G (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

324 TQ -OCH ₂ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ COOH

325 TQ -OCH ₂ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

326 TQ-OGH ₂ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH

327 TQ -OCH ₂ -H 9 -C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

328 TQ -OCH ₂ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

329 TQ -OCH ₂ -H 9-C (CH ₃ ) ₂ OH -SC (CH ₃ ) ₂ CH ₂ COOH

330 TQ -OCH ₂ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

331 TQ -OCH ₂ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

332 Q -OCH ₂ -HH -SCH ₂ CH ₂ COOH

333 Q -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

334 Q -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

335 Q -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

336 4-CI-Q -OCH ₂ -HH -SCH ₂ CH ₂ COOH

337 4-CI-Q -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

338 4-CI-Q -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

339 4-CI-Q -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

340 5-FQ-OGH ₂ -HH -SCH ₂ CH ₂ COOH

341 5-FQ -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

342 5-FQ -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

343 5-FQ -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

344 7-CF3-Q -OCH ₂ -HH -SCH ₂ CH ₂ COOH

345 7-CF3-Q-OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

346 7-CF3-Q -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

347 7-CF3-Q -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

348 5,7-diF-Q -OCH ₂ -HH -SCH ₂ CH ₂ COOH

349 5,7-diF-Q -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

350 5,7-diF-Q -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

351 5,7-diF-Q -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

352 6-F, 7- CF ₃ -Q -OCH ₂ -HH -SCH ₂ CH ₂ COOH

353 6-F.7-GF ₃ -Q-OGH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

354 6-F, 7-CF ₃ -Q -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

355 6- F, 7-CF ₃ -Q -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

356 5,6,7-triF-Q-OGH ₂ -HH -SCH ₂ CH ₂ COOH 357 5,6J-triF-Q -OCH ₂ -HH-SCH ₂ CH (CH ₃ ) COOH

358 5,6,7-triF-Q -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

359 5,6,7-triF-Q-OGH ₂ -HH-SCH ₂ C (CH ₂ GH ₂ ) CH ₂ COOH

360 4-t-Bu-T -OCH ₂ -HH -SCH ₂ CH ₂ COOH

361 4-t-Bu-T -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

362 4-t-Bu-T -OCH ₂ -HH-SCH ₂ C (CH ₃ ) ₂ COOH

363 4-t-Bu-T -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

364 5-F-BT -OCH ₂ -HH -SCH ₂ CH ₂ COOH

365 5-F-BT -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

366 5-F-BT -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

367 5-F-BT -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

368 5,6-diF-BT -OCH ₂ -HH -SCH ₂ CH ₂ COOH

369 5,6-diF-BT-OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

370 5,6-diF-BT -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

371 5,6-diF-BT -OCHj- HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

372 5-F-BO-OCH ₂ -HH -SCH ₂ CH ₂ COOH

373 5-F-BO -OCH ₂ -HH-SCH ₂ CH (CH ₃ ) COOH

374 5-F-BO -OCH ₂ -HH-SCH ₂ C (GH ₃ ) ₂ COOH

375 5-F-BO -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

376 6-t-Bu-Py -OCH ₂ -HH -SCH ₂ CH ₂ COOH

377 6-t-Bu-Py -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

378 6-t-Bu-Py -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

379 6-t-Bu-Py -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

380 5-Me, 6 + P 「-OCH ₂ -HH -SCH ₂ CH ₂ COOH

 Py

381 5-Me, 6-iP _{"-OCH 2 - HH -SCH 2 CH (} CH 3) COOH

 Py

382 5-Me, 6-i-Pi ^ -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

 Py

383 5-Me, 6-iP _{"-OCH 2 - HH -SCH 2 C (} CH 2 CH 2) CH 2 COOH

Py

384 6,7-diF-Q — GH2GH2HH -SCH ₂ CH ₂ COOH

385 6,7-diF-Q i GH ₂ GH2-HH -SCH ₂ CH (CH ₃ ) COOH

386 6,7-diF-Q i GH ₂ GH2-HH -SCH ₂ C (CH ₃ ) ₂ COOH

387 6J-diF- Q one _{CH2GH2- HH -SCH 2 C (CH 2} CH 2) CH 2 COOH

388 6,7-diF-Q one GH CHs one HH -SCH ₂ CH ₂ COOH

389 6-F.7-CI-Q-CHgCHs— HH -SCH ₂ CH (CH ₃ ) COOH

390 6-FJ-C Q Q GHgGH— HH -SCH ₂ C (CH ₃ ) ₂ COOH

391 6-FJ-G Q Q H2 H- HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

392 7-FQ over Li H ₂ City H2 - HH -SCH ₂ CH ₂ COOH

393 7-FQ R-H-HH -SCH ₂ CH (CH ₃ ) COOH

394 7-FQ ~ CH ₂ Oho ^— HH -SCH ₂ C (CH ₃ ) ₂ COOH

395 7-FQ i CH ₂ Ghi2— HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

396 TQ — H H2 HH -SCH ₂ CH ₂ COOH

397 TQ One H Hs One HH -SCH ₂ CH (CH ₃ ) COOH

398 TQ One H H2 One HH -SCH ₂ C (CH ₃ ) ₂ COOH u

 Π2 1

/ all Π Π b H ₂ H ₂

Ό, / air Π Π Π Π2 Π Π3 Π

 4U o air w Π Π Π — QPW i PH PH r »n OH

 Π2 2 1 2 2 β "7— rli — Π u

 ri 1 Π 0 Π2 ri υπ

 11 n _cr; u pu pu ^ Ρ, ^ ΠΗ 11 Π risVj rig υπ

-OH Π— μ H igijng υν \ Q -CM c-one 11 u

 θν

 —Γ \ u u

/ air j Π n Π ₂ Π π ₃ Π u

 * t 1 u Π2 11 Π lis Π3 2

 4111 H n

1 / Qlr —

* t I ς 0 D, / air — nr * w ― Π Pi 11 Π2 Π Π ₃ VJ jn

410 D, / "· αΐΓ — Uϊ * Ι M-Ιs 一 71-1 U i-J

_Q u ΡΠΠΙ-Ι

 4 n one ΠΠΗ —

 u

Π Π2 .ΗίΌΗ Π3 f * nnH

 Π2 Π2 Π3 2

 u

 o, / air 2 Π 0 rigUn r Π ¾Η

 / air -Π Ι-Ι2― μι

 O 1

 * t fi 0, 7 / -H aiiFr-Ox -O ^ H-one u 1 i Un _% cj u n 2 Ρ Ρ _ /, Η 2 ΓϊΗ □ 2 ΓίΠΠΗ ΓίΠΠΗ

4 β o, / air ii Π * Η ― u

 Π

 u Q_pu ΠΗ -cpu ΠΗίΌ.Η 3 Ρ, ΠΠΗ fi 7-HiF-O H Q-ΠΗ OH -Q u '2 ΠΗ1 Ρ, Η 1 Ρ, Η3 IfiOOH 1 / air -ΠΡΗu

 11 Π2-/ fl2 2

 u, / air -Π Μ ri ― u

 1

 4 4

4 -ΠΡΗ ― Π2 Π «rig

 -Π ^ Η0-u Q_pu ΠΜ

 -J o, air Jl 1 11 ο \ _ Π2 η η 2 υ η μι 7_pu— u

 * f O / ulr 2 Π / Π— L ri2 Ο Π2 υ π

 * O vx -ΠΡΗ ― 11 / \ l Π2 O Π2 Π2 Π

 Π

D, / Qlr — Π Ι Π-Ι2― 11 7-P -P Π ₂ ΰ Π2 Π3 2

441 6,7-diF-Q-0CH ₂ -H 7—〇Η = 〇Η ₂ -SC (CH ₃ ) ₂ CH ₂ COOH

442 6,7-diF-Q-0CH ₂ -H 7-CH = CH ₂ -SCH ₂ CH (CH ₃ ) CH ₂ COOH

443 6,7-diF-Q-0CH ₂ -H 7-CH = CH ₂ -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

444 6,7-diF-Q 1 0GH ₂ -H 8-CH = CH ₂ -SCH ₂ C00H 445 6,7-diF-Q -OCH ₂ -H 8-CH = GH ₂ -SCH ₂ CH ₂ COOH

446 6,7-diF-Q -OCH ₂ -H 8-CH = CH ₂ -SCH ₂ CH (CH ₃ ) COOH

447 6J-diF-Q -OCH ₂ -H 8-CH = CH ₂ -SCH ₂ CH (CH ₂ CH ₃ ) COOH

448 6,7-diF-Q-OCH ₂ -H 8-CH = CH ₂ -SCH ₂ C (CH ₃ ) ₂ COOH

449 6,7-diF-Q -OCH ₂ -H 8-CH = CH ₂ -SC (CH ₃ ) ₂ CH ₂ COOH

450 6,7-diF-Q-OGH ₂ -H 8-CH = CH ₂ -SCH ₂ CH (CH ₃ ) CH ₂ COOH

451 6J-diF-Q -OCH ₂ -H 8-CH = CH ₂ -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

452 6,7-diF-Q -OCH ₂ -H 9-CH = CH ₂ -SCH ₂ COOH

453 6,7-diF-Q -OCH ₂ -H. 9-CH = CH ₂ -SCH ₂ CH ₂ COOH

454 6,7-diF-Q -OCH ₂ -H 9-CH = CH ₂ -SCH ₂ CH (CH ₃ ) COOH

455 6J-diF-Q -OCH ₂ -H 9-CH = CH ₂ -SCH ₂ CH (CH ₂ CH ₃ ) COOH

456 6,7-diF-Q -OCH ₂ -H 9-CH = CH ₂ -SCH ₂ C (CH ₃ ) ₂ COOH

457 6,7-diF-Q -OCH ₂ -H 9-CH = CH ₂ -SC (CH ₃ ) ₂ CH ₂ COOH

458 6,7-diF-Q-OCH ₂ -H 9-CH = CH ₂ -SCH ₂ CH (CH ₃ ) CH ₂ COOH

459 6,7-diF-Q-OGH ₂ -H 9-CH = CH ₂ -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

460 6,7-diF-Q -OCH ₂ -H 7-OCH ₃ -SCH ₂ COOH

461 6J-diF-Q -OCH ₂ -H 7-OCH3 -SCH ₂ CH ₂ COOH

462 6,7-diF-Q -OCH ₂ -H 7-OCH3 -SCH ₂ CH (CH ₃ ) COOH

463 6,7-diF-Q -OCH ₂ -H 7-OCH3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

464 6,7-diF-Q -OCH ₂ -H 7-OCH3 -SCH ₂ C (CH ₃ ) ₂ COOH

465 6,7-diF-Q-OGH ₂ -H 7-OCH3 -SC (CH ₃ ) ₂ CH ₂ COOH

466 6,7-diF-Q -OCH ₂ -H 7-OCH3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

467 6,7-diF-Q -OCH ₂ -H 7-OCH3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

468 6,7-diF-Q -OCH ₂ -H 8-OCH3 -SCH ₂ COOH

469 6,7-diF-Q -OCH ₂ -H 8-OCH3 -SCH ₂ CH ₂ COOH

470 6,7-diF-Q -OCH ₂ -H 8-OCH3 -SCH ₂ CH (CH ₃ ) COOH

471 6J-diF-Q -OCH ₂ -H 8-OCH3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

472 6,7-diF-Q -OCH ₂ -H 8-OCH3 -SCH ₂ C (CH ₃ ) ₂ COOH

473 6,7-diF-Q -OCH ₂ -H 8-OCH3 -SC (CH ₃ ) ₂ CH ₂ COOH

474 6,7-diF-Q -OCH ₂ -H 8-OCH3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

475 6J-diF-Q -OCH ₂ -H 8-OCH3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

476 6J-diF-Q-OGH ₂ -H 9-OCH3 -SCH ₂ COOH

477 6,7-diF-Q -OCH ₂ -H 9-OCH ₃ -SCH ₂ CH ₂ COOH

478 6,7-diF-Q -OCH ₂ -H 9-OCH3 -SCH ₂ CH (CH ₃ ) COOH

479 6,7-diF-Q-OGH ₂ -H 9-OCH3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

480 6,7-diF-Q-OCH ₂ -H 9-OCH3 -SCH ₂ C (CH ₃ ) ₂ COOH

481 6,7-diF-Q-OCH ₂ -H 9-OCH3 -SC (CH ₃ ) ₂ CH ₂ COOH

482 6,7-diF-Q -OCH ₂ -H 9-OCH3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

483 6,7-diF-Q -OCH ₂ -H 9-OCH3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

484 6,7-diF-Q -OCH ₂ -H 7-OCHF ₂ -SCH ₂ COOH

485 6,7-diF-Q -OCH ₂ -H 7-OGHF ₂ -SCH ₂ CH ₂ COOH

486 6,7-diF-Q -OCH ₂ -H 7-OCHF ₂ -SCH ₂ CH (CH ₃ ) COOH

487 6,7-diF-Q -OCH ₂ -H 7-OCHF ₂ -SCH ₂ CH (CH ₂ CH ₃ ) COOH

488 6,7-diF-Q -OCH ₂ -H 7-OCHF ₂ -SGH ₂ C (CH ₃ ) ₂ COOH

489 6,7-diF-Q -OCH ₂ -H 7-OCHF ₂ -SC (GH ₃ ) ₂ CH ₂ COOH

490 6,7-diF-Q i OCH ₂ -H 7-OCHF ₂ -SCH ₂ CH (CH ₃ ) CH ₂ COOH

40 u _t air — ΠΡΙ-Ι ―

 ΠΙ n

Ηϊ Ο -ΠΡ.Η1 μ π ft-OP.HP

 One μ ft _cr; u

 fi 7-HiF-O -ΠΠΗ1 μ

 O

 -ΠΠΗone Η -SOH Γ ΠΗ ΟΩΠΗ

-ΠΠΗ 一 Η

 One ΠΠΗ— Η one SOH fiHCfiH) CM ΠΠΠΗ fi 7— HiF— one snhLfiffihLnHJriH

 Q-DOHF -QOH ΩΠΗ

 u

 U I 1

 OU 0, / air -ΠΡΙ-Ι ― u

 Π Π

 D, / air — n w- u π O uun

OUD D _t / air one n * w― yn 0 Π Pig

 OUO Ό, / U 3 nt i Π Π

OU / 0 air — H W1 μι Q— nPW Π

OUO β 0, rlipr— Π -Π Ι-Ι ― / U 1?

 o,, air -ΠΡΜ ri one π

 Ό I U a 0, pr— n -OPW ― μ

 π _c u ^, πΠΗ

-ΠΡ.Η 一

 67— HiF— Ω -ΠΟΗone Η / v «one SnhL i iH) ΠΩΠΗ

J ow -ΠΡ.Η 一 Η π 3 η 3 2 η 2 »« η

«J -ΠΡ.Η1 Η, Η ΟΗίΌΗ ^ ΟΗ ^ ΟΩΩΗ Lily -ΠΠΗ1 Η" 7-OG

 u-OOH-πQ-OP.F

 -ΠΓϊΗ 一 Η

 o -ΠΠΗ1 μ -COH ΠΗίΉΗ 1ΠΩΠΗ η

51 Q fi 7-WiF-O π o η η μ π -OP.F

 H 0, -ΠΡΗ 一 u

 O o n ri n n u ri coo fi 7— rliF-n — ΠΡΙ-Ι ― μ

 Ο rig n u u n 07— C— Π —now— υ

 o, / air j — ΠΡΙ-Ι 一 u π O U Ji 1

 3 0 o, / air — now one π U -Q H PN * I-I ΡΠΠΗ

5 Kufu -ΠΡ ― μ π Q-Π UΠΡ _cpu ΠΗΓΓϊΗ fin ΊΠΠΠΗ

5k β -Π μ

 UΡΜ ri one π

 -ΠΡ.Η― -ΠΠΡ SfYfiH 1 CM Ρ.ΠΠΗ 7-HiF-O -ΩΠΗ «--SGH GH (GH GH GOOH

531 67— diF-Q-1 0〇Η ₂ -Η 9-OCF3 SCH C (CH GH) GH G00H

532 67-diF-O Η 7-SOCH -SCH.C00H

533 6,7-diF-Q-0GH ₂ -Η 7-SOCH3 -SCH ₂ CH ₂ COOH

534 6,7-diF-Q-0GH ₂ -Η 7-SOCH3 -SCH ₂ CH (CH ₃ ) COOH

535 6,7-diF-Q-0GH ₂ -Η 7-SOCH3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

536 6,7-diF-Q-0CH ₂ -Η 7-SOCH3 -SCH ₂ C (CH ₃ ) ₂ COOH 537 6,7-diF-Q-OCH ₂ -H 7- -SOCH ₃ -SC (CH ₃ ) ₂ CH ₂ COOH

538 6,7-diF-Q -OCH ₂ -H 7- -SOCH3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

539 6,7-diF-Q -OCH ₂ -H 7- SOCH3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

540 6,7-diF-Q -OCH ₂ -H 8- -SOCH3 -SCH ₂ COOH

541 6,7-diF-Q -OCH ₂ -H 8- -SOCH3 -SCH ₂ CH ₂ COOH

542 6,7-diF-Q-OGH ₂ -H 8- SOCH3 -SCH ₂ CH (CH ₃ ) COOH

543 6,7-diF-Q -OCH ₂ -H 8-SOCH3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

544 6,7-diF-Q-OCH ₂ -H 8- SOCH3 -SCH ₂ C (CH ₃ ) ₂ COOH

545 6J-diF-Q-OCH ₂ -H 8-SOCH3 -SC (CH ₃ ) ₂ CH ₂ COOH

546 6,7-diF-Q -OCH ₂ -H 8-SOCH3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

547 6J-diF-Q-OCH ₂ -H 8- -SOCH3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

548 6,7-diF-Q -OCH ₂ -H 9- SOCH3 -SCH ₂ COOH

549 6,7-diF-Q -OCH ₂ -H 9- ■ SOCH ₃ -SCH ₂ CH ₂ COOH

550 6J- diF-Q -OCH ₂ -H 9- SOCH3 -SCH ₂ CH (CH ₃ ) COOH

551 6,7-diF-Q-OCH ₂ -H 9- -SOCH3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

552 6,7-diF-Q -OCH ₂ -H 9- -SOCH3 -SCH ₂ C (CH ₃ ) ₂ COOH

553 6,7-diF-Q-OCH ₂ -H 9- SOCH3 -SC (CH ₃ ) ₂ CH ₂ COOH

554 6,7-diF-Q-OCH ₂ -H 9- -SOCH3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

555 6,7-diF-Q -OCH ₂ -H 9- -SOCH3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

556 6,7-diF-Q-OCH ₂ -H 7- -S0 ₂ CH ₃ -SCH ₂ COOH

557 6,7-diF-Q-OCH ₂ -H 7- S0 ₂ CH ₃ -SCH ₂ CH ₂ COOH

558 6,7-diF-Q-OCH ₂ -H- -S0 ₂ CH ₃ -SCH ₂ CH (CH ₃ ) COOH

559 6,7-diF-Q-OCH ₂ -H 7- -S0 ₂ CH ₃ -SCH ₂ CH (CH ₂ CH ₃ ) COOH

560 6J-diF-Q-OCH ₂ -H 7- -S0 ₂ CH ₃ -SCH ₂ C (CH ₃ ) ₂ COOH

561 6J-diF-Q -OCH ₂ -H 7- -S0 ₂ CH ₃ -SC (CH ₃ ) ₂ CH ₂ COOH

562 6,7-diF-Q -OCH ₂ -H 7- -S0 ₂ CH ₃ -SCH ₂ CH (CH ₃ ) CH ₂ COOH

563 6J-diF-Q-OGH ₂ -H 7- -S0 ₂ CH ₃ -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

564 6J-diF-Q-OGH ₂ -H 8- -S0 ₂ CH ₃ -SCH ₂ COOH

565 6J-diF-Q -OCH ₂ -H 8- -S0 ₂ CH ₃ -SCH ₂ CH ₂ COOH

566 6,7-diF-Q-OGH ₂ -H 8- -S0 ₂ CH ₃ -SCH ₂ CH (CH ₃ ) COOH

567 6,7-diF-Q-OGH ₂ -H 8- -S0 ₂ CH ₃ -SCH ₂ CH (CH ₂ CH ₃ ) COOH

568 6,7-diF-Q-OGH ₂ -H 8- S0 ₂ CH ₃ -SCH ₂ C (CH ₃ ) ₂ COOH

569 6,7-diF-Q-OGH ₂ -H 8- -S0 ₂ CH ₃ -SC (CH ₃ ) ₂ CH ₂ COOH

570 6,7-diF-Q-OGH ₂ -H 8--S0 ₂ CH ₃ -SCH ₂ CH (CH ₃ ) CH ₂ COOH

571 6,7-diF-Q-OCH ₂ -H 8- -S0 ₂ CH ₃ -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

572 6,7-diF-Q -OCH ₂ -H 9- -S0 ₂ CH ₃ -SCH ₂ COOH

573 6,7-diF-Q-OGH ₂ -H 9- -S0 ₂ CH ₃ -SCH ₂ CH ₂ COOH

574 6J-diF-Q -OCH ₂ -H 9- -S0 ₂ CH ₃ -SCH ₂ CH (CH ₃ ) COOH

575 6,7-diF-Q -OCH ₂ -H 9- -S0 ₂ CH ₃ -SCH ₂ CH (CH ₂ CH ₃ ) COOH

576 6,7-diF-Q -OCH ₂ -H 9- -S0 ₂ CH ₃ -SCH ₂ C (CH ₃ ) ₂ COOH

577 6,7-diF-Q -OCH ₂ -H 9- -S0 ₂ CH ₃ -SC (CH ₃ ) ₂ CH ₂ COOH

578 6,7-diF-Q -OCH ₂ -H 9- -S0 ₂ CH ₃ -SCH ₂ CH (CH ₃ ) CH ₂ COOH

579 6,7-diF-Q-OGH ₂ -H 9- -S0 ₂ CH ₃ -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

580 6,7-diF-Q - OGH 2 - 1 -FH - SCH 2 COOH

_{581 6,7-diF-Q -OCH 2} - 1 -FH -SCH 2 CH 2 COOH

_{582 6,7-diF-Q -OCH 2} - 1 -FH -SCH 2 CH (CH 3) COOH oo fi 7-HiF-n -ΠΓ * Η 一 1-u

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fi 7— diF— Ω -non-1 4- -QHH ΟΗ ΊΟ ΊΟ, ΠΠΗ fi 7-HiF-O -ηπΗ-1 H 1 -QOH ΠΗ 1 Γ ΟΗ ΟΗ ^ ΟΩΩΗ fi 7-HiF-O H _cpu p pu ΠΠΠΗ β DΠU1 I o _t / air I one nw ri- un 1 uu ^ u

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n _c u ρ, ΗίΤ.Η ^ ΓϊΠΠΗ fi1 R fi 7-HiF-n \ J one -COH ΟΗίΉΗ ΠΗ 'ΙΩΩΗ fi 7-HiF-O vx -ηπΗone • 3- -CA H 1 one SGhL ifGH GOOH

-ΠΟΗ 一 -Ol H 11

 619 -OCH-3- -CI H-I SGH G (GH Gh CH C00H

620 67-HiF-O 4- -CI H -SCHoCOOH

621 g 7-Jj -Q _QQ | _ | ₂ _ 4- -CI H one SGH GH G00H

_{622 g -Jj -Q -0CH 2 - 4-} -CI H one SCHoGH (GH G00H

_{623 6,7-diF-Q -0CH 2} - 4- -CI H one SGH, GH (GH GH,) G00H n -Q0H CfCH) 0ΩΩΗ

_{625 6,7-diF- Q -0CH 2 -} 4- -CI H -SC (CH 3) 2 CH 2 COOH

626 6,7-diF-Q - 0GH 2 - 4- -CI H -SCH 2 CH (CH 3) CH 2 COOH

627 6,7-diF-Q - 0CH 2 - 4- -CI H -SCH 2 C (CH 2 CH 2) CH 2 COOH

_{628 6,7-diF-Q -0CH 2} - 1- -N0 2 H -SCH 2 C00H _{629 6,7-diF-Q -OCH 2} - 1 - -N0 2 H -SCH 2 CH 2 COOH

_{630 6,7-diF-Q -OCH 2} - 1 - -N0 2 H -SCH 2 CH (CH 3) COOH

631 6,7-diF-Q - OCH 2 - 1 - -N0 2 H -SCH 2 CH (CH 2 CH 3) COOH

632 6,7-diF-Q - OCH 2 - 1 - -N0 2 H -SCH 2 C (CH 3) 2 COOH

633 6,7-diF-Q - OCH 2 - 1 - -N0 2 H -SC (CH 3) 2 CH 2 COOH

_{634 6,7-diF-Q -OCH 2} - 1 - -N0 2 H -SCH 2 CH (CH 3) CH 2 COOH

_{635 6,7-diF-Q -OCH 2} - 1 - -N0 2 H -SCH 2 C (CH 2 CH 2) CH 2 COOH

636 6,7-diF-Q - OCH 2 - 3- -N0 2 H - SCH 2 COOH

_{637 6,7-diF-Q -OCH 2} - 3- -N0 2 H -SCH 2 CH 2 COOH

_{638 6J - diF- Q - OCH 2} - 3- -N0 2 H - SCH 2 CH (CH 3) COOH

_{639 6,7- diF - Q - OCH 2} - 3- -N0 2 H -SCH 2 CH (CH 2 CH 3) COOH

_{640 6,7-diF-Q -OCH 2} - 3- -N0 2 H -SCH 2 C (CH 3) 2 COOH

641 6,7-diF-Q - OCH 2 - 3- -N0 2 H -SC (CH 3) 2 CH 2 COOH

_{642 6,7-diF-Q -OCH 2} - 3- -N0 2 H -SCH 2 CH (CH 3) CH 2 COOH

_{643 6,7-diF-Q -OCH 2} - 3- -N0 2 H -SCH 2 C (CH 2 CH 2) CH 2 COOH

_{644 6,7-diF-Q -OCH 2} - 4- -N0 2 H -SCH 2 COOH

645 6,7-diF-Q - OCH 2 - 4- -N0 2 H -SCH 2 CH 2 COOH

646 6,7-diF-Q - OCH 2 - 4- -N0 2 H -SCH 2 CH (CH 3) COOH

647 6,7-diF-Q - OCH 2 - 4- -N0 2 H -SCH 2 CH (CH 2 CH 3) COOH

648 6,7-diF-Q - OGH 2 - 4- -N0 2 H -SCH 2 C (CH 3) 2 COOH

649 6,7-diF-Q - OCH 2 - 4- -N0 2 H - SG (CH 3) 2 CH 2 COOH

650 6,7-diF-Q - OCH 2 - 4- -N0 2 H -SCH 2 CH (CH 3) CH 2 COOH

_{651 6,7-diF-Q -OCH 2} - 4- -N0 2 H -SCH 2 C (CH 2 CH 2) CH 2 COOH

_{652 6J-diF-Q -OCH 2} - 1 - -CN H - SCH 2 COOH

_{653 6,7-diF-Q -OCH 2} - 1 - -CN H -SCH 2 CH 2 COOH

_{654 6,7-diF-Q -OCH 2} - 1 - -CN H -SCH 2 CH (CH 3) COOH

_{655 6,7-diF-Q -OCH 2} - 1 - -CN H - SCH 2 CH (CH 2 GH 3) COOH

_{656 6,7-diF-Q -OCH 2} - 1 - -CN H -SCH 2 C (CH 3) 2 COOH

657 6,7-diF-Q - OCH 2 - 1 - -CN H -SC (CH 3) 2 CH 2 COOH

658 6,7-diF-Q - OCH 2 - 1 - -CN H -SCH 2 CH (CH 3) CH 2 COOH

_{659 6,7-diF-Q _OCH 2} - 1 - -CN H -SCH 2 C (CH 2 CH 2) CH 2 COOH

_{660 6J- diF-Q - OGH 2} - 3- -CN H -SCH 2 COOH

661 6,7-diF-Q - OGH 2 - 3- -CN H -SCH 2 CH 2 COOH

_{662 6,7-diF-Q -OCH 2} - 3- -CN H -SCH 2 CH (CH 3) COOH

_{663 6,7-diF-Q -OCH 2} - 3- -CN H -SCH 2 CH (CH 2 CH 3) COOH

_{664 6,7-diF-Q -OCH 2} - 3- -CN H -SCH 2 C (CH 3) 2 COOH

_{665 6,7-diF-Q -OCH 2} - 3- -CN H -SC (CH 3) 2 CH 2 COOH

_{666 6J - diF- Q - OCH 2} - 3- -CN H -SCH 2 CH (CH 3) CH 2 COOH

_{667 6,7-diF-Q -OCH 2} - 3- -CN H -SCH 2 C (CH 2 CH 2) CH 2 COOH

668 6,7-diF-Q - OCH 2 - 4- -CN H - SCH 2 COOH

_{669 6,7-diF-Q -OCH 2} - 4- -CN H -SCH 2 CH 2 COOH

670 6,7-diF-Q -OCHj- 4- -CN H -SCH ₂ CH (CH ₃ ) COOH

_{671 6,7-diF-Q -OCH 2} - 4- -CN H -SCH 2 CH (CH 2 CH 3) COOH

_{672 6,7-diF-Q -OCH 2} - 4- -CN H -SCH 2 C (CH 3) 2 COOH

_{673 6,7-diF-Q -OCH 2} - 4- -CN H -SC (CH 3) 2 CH 2 COOH

674 6,7-diF-Q one _{OCH 2 - 4- -CN H -SCH 2} CH (CH 3) CH 2 COOH 675 6,7-diF-Q -OCH _2-4 -CN H -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

_{676 6,7-diF-Q -OCH 2} - 1 - ■ CH 3 H -SCH 2 COOH

677 6,7-diF-Q - OCH 2 - 1 - ■ CH 3 H -SCH 2 CH 2 COOH

678 6,7-diF-Q - OCH 2 - 1 - ■ CH 3 H -SCH 2 CH (CH 3) COOH

_{679 6,7-diF-Q -OCH 2} - 1 - -CH 3 H -SCH 2 CH (CH 2 CH 3) COOH

_{680 6,7-diF-Q -OCH 2} - 1 - CH 3 H -SCH 2 C (CH 3) 2 COOH

681 6,7-diF-Q - OGH 2 - 1 - ■ CH 3 H -SC (CH 3) 2 CH 2 COOH

_{682 6J-diF-Q -OCH 2} - 1 - -CH 3 H -SCH 2 CH (CH 3) CH 2 COOH

683 6,7-diF-Q - OCH 2 - 1 - ■ CH 3 H -SCH 2 C (CH 2 CH 2) CH 2 COOH

684 6,7-diF-Q - OGH 2 - 3- -CH 3 H -SCH 2 COOH

_{685 6,7-diF-Q -OCH 2} - 3- ■ CH 3 H -SCH 2 CH 2 COOH

686 6,7-diF-Q - OCH 2 - 3- -CH 3 H -SCH 2 CH (CH 3) COOH

_{687 6,7-diF-Q -OCH 2} - 3- ■ CH 3 H -SCH 2 CH (CH 2 CH 3) COOH

_{688 6,7-diF-Q -OCH 2} - 3- ■ CH 3 H -SCH 2 C (CH 3) 2 COOH

_{689 6,7-diF-Q -OCH 2} - 3- ■ CH 3 H -SC (CH 3) 2 CH 2 COOH

_{690 6,7-diF-Q -OCH 2} - 3- ■ CH 3 H -SCH 2 CH (CH 3) CH 2 COOH

_{691 6,7-diF-Q -OCH 2} - 3- -CH 3 H -SCH 2 C (CH 2 CH 2) CH 2 COOH

_{692 6J-diF-Q -OCH 2} - 4- -CH 3 H -SCH 2 COOH

_{693 6J-diF-Q -OCH 2} - 4- -CH 3 H -SCH 2 CH 2 COOH

694 6,7-diF-Q - OCH 2 - 4- -CH 3 H -SCH 2 CH (CH 3) COOH

695 6,7-diF-Q - OCH 2 - 4- -CH 3 H -SCH 2 CH (CH 2 CH 3) COOH

_{696 6,7-diF-Q -OCH 2} - 4- -CH 3 H - SCH 2 C (CH 3) 2 GOOH

_{697 6,7-diF-Q -OCH 2} - 4- -CH 3 H -SC (CH 3) 2 CH 2 COOH

_{698 6J-diF-Q -OCH 2} - 4- -CH 3 H -SCH 2 CH (CH 3) CH 2 COOH

_{699 6,7-diF-Q -OCH 2} - 4- -CH 3 H -SCH 2 C (CH 2 CH 2) CH 2 COOH

_{700 6,7- diF- Q - OCH 2 -} 1 - -OCH 3 H -SCH 2 COOH

_{701 6,7-diF-Q -OCH 2} - 1 - -OCH3 H -SCH 2 CH 2 COOH

_{702 6,7- diF- Q -OCH 2 - 1} - -OCH3 H -SCH 2 CH (CH 3) COOH

703 6,7-diF-Q - OCH 2 - 1 - -OCH3 H -SCH 2 CH (CH 2 CH 3) COOH

704 6,7-diF-Q - OCH 2 - 1 - -OCH3 H -SCH 2 C (CH 3) 2 COOH

_{705 6,7-diF-Q -OCH 2} - 1 - -OCH3 H -SC (CH 3) 2 CH 2 COOH

_{706 6,7-diF-Q -OCH 2} - 1 - -OCH3 H -SCH 2 CH (CH 3) CH 2 COOH

_{707 6,7-diF-Q -OCH 2} - 1 - -OCH3 H -SCH 2 C (CH 2 CH 2) CH 2 COOH

_{708 6J-diF-Q -OCH 2} - 3- -OCH3 H -SCH 2 COOH

709 6,7-diF-Q - OGH 2 - 3- -OCH3 H -SCH 2 CH 2 COOH

_{710 6,7-diF-Q -OCH 2} - 3- -OCH3 H -SCH 2 CH (CH 3) COOH

71 1 6,7-diF-Q -OCH 2 - 3- -OCH3 H -SCH 2 CH (CH 2 CH 3) COOH

712 6,7-diF-Q - OGH 2 - 3- -OCH3 H -SCH 2 C (CH 3) 2 COOH

_{713 6,7-diF-Q -OCH 2} - 3- -OCH3 H -SC (CH 3) 2 CH 2 COOH

_{714 6,7-diF-Q -OCH 2} - 3- -OCH3 H -SCH 2 CH (CH 3) CH 2 COOH

_{715 6,7-diF-Q -OCH 2} - 3- -OCH3 H -SCH 2 C (CH 2 CH 2) CH 2 COOH

716 6,7-diF-Q - OGH 2 - 4- -OCH 3 H -SCH 2 COOH

71 7 6,7-diF-Q - OCH 2 - 4- -OCH3 H -SCH 2 CH 2 COOH

718 6,7-diF-Q - OCH 2 - 4- -OCH3 H -SCH 2 CH (CH 3) COOH

719 6J-diF-Q - OCH 2 - 4- -OCH3 H -SCH 2 CH (CH 2 CH 3) COOH

_{720 6J- diF- Q -OCH 2 - 4-} -OCH3 H -SCH 2 C (CH 3) 2 COOH 721 6,7-diF-Q - OCH 2 - 4- OCH 3 H -SC (CH 3) 2 CH 2 COOH

722 6J-diF-Q - OCH 2 - 4- H -SCH 2 CH (CH 3) CH 2 COOH

723 6,7-diF-Q - OCH 2 - 4- OCH 3 H -SCH 2 C (CH 2 CH 2) CH 2 COOH

724 6,7-diF-Q — GH CHs-HH -SCH ₂ COOH

725 6,7-diF-Q — GH2GH2-HH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

726 6,7-diF-Q i CH GH-HH -SC (CH ₃ ) ₂ CH ₂ COOH

727 6J-diF-Q — GH2GH2— HH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

728 6,7-diF-Q One H ₂ One H 7- F -SCH ₂ COOH

729 6,7-diF-Q 1 GH-H 7-F-SCH ₂ CH ₂ COOH

730 6J-diF-Q ^— Gri V- / H2 ^— H 7- F -SCH ₂ CH (CH ₃ ) COOH

731 6J-diF-Q H2 then H2—H7-F-SCH ₂ CH (CH ₂ CH ₃ ) COOH

732 6,7-diF-Q Mushroom H— H 7- -F -SCH ₂ C (CH ₃ ) ₂ COOH

733 6,7-diF-Q chromatography Li H2 Mr H2- H 7- ■ F -SC (CH 3) 2 CH 2 COOH

734 6,7-diF-Q i H — H 7- ■ F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

735 6,7-diF-Q i GH uH— H 7- F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

736 6,7-diF-Q 1 Hg—H 8-F-SCH ₂ COOH

737 6J-diF-Q One H ₂ shi — H 8- ■ F -SCH ₂ CH ₂ COOH

738 6J-diF - Q one GH one _{H 8- F -SCH 2 CH (CH} 3) COOH

739 6,7-diF-Q one H 8-F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

740 6,7-diF-Q lysed Hg— H 8- -F -SCH ₂ C (CH ₃ ) ₂ COOH

741 6J-diF-Q H2 then H2 H 8- F -SC (CH ₃ ) ₂ CH ₂ COOH

742 6,7-diF-Q — GH-H 8- -F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

743 6,7-diF-Q — GH Hs-H 8- -F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

744 6J-diF-Q One GH Re Hs One H 9- -F -SCH ₂ COOH

745 6J-diF-Q —GHs Li H 9- -F -SCH ₂ CH ₂ COOH

746 6J-diF-Q — GHs H ₂ -H 9- -F -SCH ₂ CH (CH ₃ ) COOH

747 6,7-diF-Q i_ H shi i H 9- -F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

748 6J- diF-Q _Ghs Re H 9- -F -SCH ₂ C (CH ₃ ) ₂ COOH

749 6,7-diF-Q 1 Gh ₂ 1 H 9- -F -SC (CH ₃ ) ₂ CH ₂ COOH

750 6,7-diF-Q 1GH H ₂ -H 9- -F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

751 6J-diF-Q one GH ₂ v_ H2 one H 9- -F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

752 6J-diF-Q One GH One H 7- -CN -SCH ₂ COOH

753 6,7-diF-Q Hs— H 7- -CN -SCH ₂ CH ₂ COOH

754 6J-diF-Q — Gh H2-I H 7- CN -SCH ₂ CH (CH ₃ ) COOH

755 6,7-diF-Q series — H 7- -CN -SCH ₂ CH (CH ₂ CH ₃ ) COOH

756 6J- diF-Q H ₂ — H 7- -CN -SCH ₂ C (CH ₃ ) ₂ COOH

757 6,7-diF-Q 1 GH 1 H 7- -CN -SC (CH ₃ ) ₂ CH ₂ COOH

H 7- -CN -SCH₂CH(CH₃)CH₂COOH758 6J-diF-Q

H 7- -CN -SCH ₂ CH (CH ₃ ) CH ₂ COOH

759 6,7-diF-Q リ HH-H 7- -CN -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

760 6J- diF-Q i GH H 8- -CN -SCH ₂ COOH

761 6,7-diF-Q 1 GH2 1 H 8--CN -SCH ₂ CH ₂ COOH

762 6,7-diF-Q is H;> is H 8- -CN -SCH ₂ CH (CH ₃ ) COOH

763 6,7-diF-Q One GH One H 8- -CN -SCH ₂ CH (CH ₂ CH ₃ ) COOH

764 6,7-diF-Q H Hs— H 8- -CN -SCH ₂ C (CH ₃ ) ₂ COOH

765 6J- diF-Q 1 GH H2 1 H 8- -CN -SC (CH ₃ ) ₂ CH ₂ COOH

766 6,7-diF-Q 1 GHg 1 H 8- -CN -SCH ₂ CH (CH ₃ ) CH ₂ COOH 767 6J-diF-Q GHgGHs— H 8-CN-SCH ₂ C (CH ₂ CH ₂ ) CH ₂ GOOH

768 6J-diF-Q ^— CH2CH2 "" H 9-CN -SCH ₂ COOH

769 6,7-diF-Q — GH GH— H 9-CN -SCH ₂ CH ₂ COOH

770 6,7-diF-Q — GH ₂ GH2-H 9-CN -SCH ₂ CH (CH ₃ ) COOH

771 6,7-diF-Q 1 GHsGHz-H 9-CN -SCH ₂ CH (CH ₂ CH ₃ ) COOH

772 6,7-diF-Q — GHsGh ^-H 9-CN -SCH ₂ C (CH ₃ ) ₂ COOH

773 6,7-diF-Q i GH ₂ GH ₂ -H 9-CN -SC (CH ₃ ) ₂ CH ₂ COOH

774 6,7-diF-Q i GH GH-H 9-CN -SCH ₂ CH (CH ₃ ) CH ₂ COOH

775 6,7-diF-Q-I GH ₂ CH2-H 9-CN -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

776 6J- diF-Q i GHgGH— H -CF3 -SCH ₂ COOH

777 6J- diF-Q i GH ₂ GH2-H -CF3 -SCH ₂ CH ₂ COOH

778 6,7-diF-Q i Grio H ₂ -H 7-CF3 -SCH ₂ CH (CH ₃ ) COOH

779 6J-diF-Q H2 and _{H 2 - H -CF3 -SCH 2 CH} (CH 2 CH 3) COOH

780 6,7-diF-Q i GH H— H -CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

781 6,7-diF-Q 1 GH2 H2-H 7-CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

782 6,7-diF-Q H ₂ then H ₂ — H 7-CF3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

783 6,7-diF-Q — GHg H 7-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

784 6,7-diF-Q — Lithium H 8-CF3 -SCH ₂ COOH

785 6,7-diF-Q H ₂ Hs 1 H 8-CF3 -SCH ₂ CH ₂ COOH

786 6,7-diF-Q H ₂ H ₂ -H 8-CF3 -SCH ₂ CH (CH ₃ ) COOH

787 6,7-diF-Q R-H-H 8-CF3- -SCH ₂ CH (CH ₂ CH ₃ ) COOH

788 6,7-diF-Q H2 then H2-H 8-CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

789 6,7-diF-Q then H ₂ -H 8-CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

790 6,7-diF-Q — GH-H 8-CF3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

791 6,7-diF-Q One GH One H 8-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

792 6,7-diF-Q i GH2UH2— H 9-CF3 -SCH ₂ COOH

793 6,7-diF-Q One GH2 One H 9-CF3 -SCH ₂ CH ₂ COOH

794 6,7-diF-Q H-H 9-CF3 -SCH ₂ CH (CH ₃ ) COOH

795 6J-diF-Q — H ₂ -H 9-CF3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

796 6,7-diF-Q One Hs One H 9-CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

797 6J-diF-Q One Hs— H 9-CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

798 6J-diF-Q 1 H ₂ H ₂ -H 9 -CF 3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

799 6,7-diF-Q H ₂ H ₂ -H 9-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

800 6,7-diF-Q One Hs then H— H 7-C = CH -SCH ₂ COOH

801 6,7-diF-Q 1 uH _2- H 7-C 3 CH -SCH ₂ CH ₂ COOH

802 6,7-diF-Q — し — H 7-C≡CH -SCH ₂ CH (CH ₃ ) COOH

803 6,7-diF-Q one C / Hg Li - H 7 - C three _{CH -SCH 2 CH (CH 2 CH} 3) COOH

804 6,7-diF-Q 1 uH ₂ Hs-H 7-C3 CH -SCH ₂ C (CH ₃ ) ₂ COOH

805 6,7-diF-Q--H 7-C3 CH -SC (CH ₃ ) ₂ CH ₂ COOH

806 6,7-diF-Q — GH H 7-G3 CH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

H 7-G三 CH -SCH₂C(CH₂CH₂)CH₂COOH807 6,7-diF-Q

H 7-G3 CH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

808 6,7-diF-Q 1 H 8-G3 CH -SCH ₂ COOH

809 6,7-diF-Q H2 1 H 8-C≡CH-SGH ₂ CH ₂ COOH

810 6,7-diF- Q リ H ₂ -H 8-G3 GH -SCH ₂ CH (CH ₃ ) COOH

81 1 6,7-diF-Q 1 H ₂ JH ₂ 1 H 8-C3 GH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

812 6J-diF-Q — H 8-C3 GH -SCH ₂ C (CH ₃ ) ₂ COOH 813 6,7-diF-Q i GH CHs-H 8-C = CH -SC (CH ₃ ) ₂ CH ₂ COOH

814 6,7-diF-Q — GHgGHs-H 8-C≡CH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

815 6,7-diF-Q — CH GH-H 8-C3 CH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

816 6,7-diF-Q 1 CH2GH2— H 9-G3 CH -SCH ₂ COOH

81 7 6,7-diF-Q i Gr ^ GH-H 9-G3 CH -SCH ₂ CH ₂ COOH

818 6,7-diF-Q one GH2CH2 - H 9 - G three _{CH -SCH 2 CH (CH 3)} COOH

819 6,7-diF-Q - GH2GH2 - H 9-G three _{CH -SCH 2 CH (CH 2 CH} 3) COOH

820 6J-diF-Q — GH2GH2— H 9-C = CH -SCH ₂ C (CH ₃ ) ₂ COOH

821 6,7-diF-Q Wash H ₂ H2-H 9-C3 CH -SC (CH ₃ ) ₂ CH ₂ COOH

822 6,7-diF-Q ^— ΟΓΊ2 * -Ή ₂ ^— H 9-G3 CH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

823 6,7-diF-Q i Gri Η ₂ -H 9-C3 CH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

824 6,7-diF-Q し₂一 H 7-C (CH ₃ ) ₂ OH -SCH ₂ COOH

825 6,7-diF-Q 1 Gri 1 H 7-C (CH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

826 6,7-diF-Q — GHs H ₂ -H 7-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH

827 6,7-diF-Q One Hs One H 7-G (GH ₃ ) ₂ OH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

828 6,7-diF-Q i Gri Hg— H 7-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

829 6,7-diF-Q then H2— H 7-C (CH ₃ ) ₂ OH -SC (CH ₃ ) ₂ CH ₂ COOH

830 6,7-diF-Q Hs then H— H 7-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

831 6,7-diF-Q 1 Grl H2 1 H 7-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

832 6J-diF-Q One-to-one H 8-C (CH ₃ ) ₂ OH -SCH ₂ COOH

833 6,7-diF-Q — GH — H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

834 6,7-diF-Q One VJH then H— H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH

835 6,7-diF-Q 1 Gri H2 1 H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

836 6,7-diF-Q — GH _2- H 8-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

837 6,7-diF-Q H2 H 1 H 8-C (CH ₃ ) ₂ OH -SC (CH ₃ ) ₂ CH ₂ COOH

838 6,7-diF-Q Hs then Hs-H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

839 6,7-diF-Q One CH One H 8-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

840 6,7-diF-Q one vjHg-H 9-C (CH ₃ ) ₂ OH -SCH ₂ COOH

841 6,7-diF-Q —H H2 H 9 -C (CH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

842 6,7-diF-Q _ H ₂ Hs-H 9-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH

843 6J-diF-Q then Hs— H 9-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

844 6,7-diF-Q "" Lily H2— H 9-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

845 6,7-diF-Q one GH one _{H 9 - C (CH 3)} 2 OH -SC (CH 3) 2 CH 2 COOH

846 6,7-diF-Q H ₂ then H ₂ — H 9 -C (GH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

847 6,7-diF-Q H ₂ H ₂ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

848 6,7-diF-Q-CH _20- HH -SCH ₂ COOH

849 6,7-diF-Q-GH _20- HH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

850 6J-diF-Q -CH ₂ 0- HH -SC (CH ₃ ) ₂ CH ₂ COOH

851 6J-diF-Q -CH ₂ 0- HH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

852 6J-diF-Q _GH ₂₀ -H 7-F-SCH ₂ COOH

853 6,7-diF-Q -GH ₂ 0-H 7-F -SCH ₂ CH ₂ COOH

854 6,7-diF-Q-GH ₂₀ -H 7-F -SCH ₂ CH (CH ₃ ) COOH

855 6,7-diF-Q-GH ₂₀ -H 7-F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

856 6J-diF-Q-GH ₂₀ -H 7-F -SCH ₂ C (CH ₃ ) ₂ COOH

857 6,7-diF-Q-CH ₂ 0_ H 7-F -SC (CH ₃ ) ₂ CH ₂ COOH

858 6,7-diF-Q-CH ₂ 0-H 7-F -SCH ₂ CH (CH ₃ ) CH ₂ COOH Q "π-0 cpu

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901 6,7-diF-Q -〇Η ₂ 0-Η 7- -CF ₃ -SCH ₂ CH ₂ COOH

902 6,7-diF-Q -〇Η ₂₀ -，,--CF ₃ -SCH ₂ CH (CH ₃ ) GOOH

903 6,7-diF-Q-CH ₂ 0-Η 7- -CF ₃ -SCH ₂ CH (CH ₂ CH ₃ ) COOH

904 6,7-diF-Q-GH ₂ 0-Η 7- -CF ₃ -SCH ₂ G (CH ₃ ) ₂ COOH 905 6J-diF-Q-CH ₂₀ -H 7-CF ₃ -SC (CH ₃ ) ₂ CH ₂ COOH

906 6J-diF-Q -CH ₂ 0- H 7-CF3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

907 6J-diF-Q-GH ₂₀ -H 7-CF ₃ -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

908 6,7-diF-Q-GH ₂₀ -H 8-CF3-SCH ₂ COOH

909 6,7-diF-Q-GH ₂₀ -H 8-CF3 -SCH ₂ CH ₂ COOH

910 6,7-diF-Q -CH ₂ 0- H 8-CF3 -SCH ₂ CH (CH ₃ ) COOH

91 1 6,7-diF-Q-CH ₂ 0-H 8-CF3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

912 6,7- diF-Q-GH ₂₀ -H 8-CF3 -SCH ₂ C (CH ₃ ) ₂ COOH

913 6,7-diF-Q -CH ₂ 0- H 8-CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

914 6,7-diF-Q-CH ₂₀ -H 8-CF3- -SCH ₂ CH (CH ₃ ) CH ₂ COOH

915 6,7-diF- Q-CH ₂ 0-H 8-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

916 6,7-diF-Q -CH ₂ 0- H 9-CF3 -SCH ₂ COOH

91 7 6,7-diF-Q -CH ₂ 0- H 9-CF3 -SCH ₂ CH ₂ COOH

918 6,7-diF-Q-GH ₂₀ -H 9-CF3 -SCH ₂ CH (CH ₃ ) COOH

919 6J-diF-Q-CH ₂₀ -H 9-CF3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

920 6,7-diF-Q-CH ₂ 0-H 9-CF3-SCH ₂ C (CH ₃ ) ₂ COOH

921 6J-diF-Q-CH ₂₀ -H 9-CF3 -SC (CH ₃ ) ₂ CH ₂ COOH

922 6J-diF-Q -CH ₂ 0- H 9-CF3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH

923 6J-diF-Q -CH ₂ 0- H 9-CF3 -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

924 6,7-diF-Q -CH ₂ 0- H 7-G3 CH -SCH ₂ COOH

925 6,7-diF-Q -CH ₂ 0- H 7-C≡CH -SCH ₂ CH ₂ COOH

926 6,7-diF-Q-GH ₂ 0-H 7-C≡CH -SCH ₂ CH (CH ₃ ) COOH

927 6J-diF-Q -CH ₂ 0- H 7-C≡CH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

928 6,7-diF-Q-CH ₂ 0-H 7-C≡CH -SCH ₂ C (CH ₃ ) ₂ COOH

929 6J- diF-Q _GH ₂ 0-H 7-G3 GH -SC (CH ₃ ) ₂ CH ₂ COOH

930 6,7-diF-Q -CH ₂ 0- H 7-C≡CH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

931 6,7-diF-Q-GH ₂ 0-H 7-C3 GH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

932 6J- diF-Q -CH ₂ 0- H 8-C3 CH-SCH ₂ COOH

933 6,7-diF-Q -CH ₂ 0- H 8-G≡CH -SCH ₂ CH ₂ COOH

934 6,7-diF-Q -CH ₂ 0- H 8-C≡CH -SCH ₂ CH (CH ₃ ) COOH

935 6,7-diF-Q-GH ₂ 0-H 8-G3 CH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

936 6,7-diF-Q-GH ₂ 0-H 8-G3 CH -SCH ₂ C (CH ₃ ) ₂ COOH

937 6,7-diF-Q - GH 2 0 - H 8 - C three _{GH -SC (CH 3) 2 CH} 2 COOH

938 6,7-diF-Q-CH ₂ 0-H 8-G3 CH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

939 6,7-diF-Q-CH ₂ 0-H 8_C3 GH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

940 6,7-diF-Q-CH _20- H 9-G3 GH -SCH ₂ COOH

941 6,7-diF-Q-CH ₂ 0-H 9-G3 CH -SCH ₂ CH ₂ COOH

942 6,7-diF-Q -CH ₂ 0- H 9 -C3 CH -SCH ₂ CH (CH ₃ ) COOH

943 6J-diF-Q -CH ₂ 0- H 9 -C3 CH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

944 6,7-diF-Q -CH ₂ 0- H 9-C = CH -SCH ₂ C (CH ₃ ) ₂ COOH

945 6,7-diF-Q -CH ₂ 0- H 9-G3 GH -SC (CH ₃ ) ₂ CH ₂ COOH

946 6,7-diF-Q -CH ₂ 0- H 9-C3 GH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

947 6,7-diF-Q-CH ₂ 0-H 9-G3 GH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

948 6J-diF-Q-GH ₂₀ -H 7-C (CH ₃ ) ₂ OH -SCH ₂ COOH

949 6,7-diF-Q -GH ₂ 0-H 7-G (GH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

950 6,7-diF-Q one _{CH 2 0 - H 7 - C} (CH 3) 2 OH -SCH 2 CH (CH 3) COOH 951 6,7-diF-Q -CH ₂ 0- H 7-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

952 6,7-diF-Q-CH ₂ 0-H 7-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

953 6,7-diF-Q-GH ₂₀ -H 7-C (CH ₃ ) ₂ OH -SC (CH ₃ ) ₂ CH ₂ COOH

954 6,7-diF-Q-CH ₂ 0-H 7-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

955 6J-diF-Q-GH ₂₀ -H 7-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

956 6,7-diF-Q -CH ₂ 0- H 8-C (CH ₃ ) ₂ OH -SCH ₂ COOH

957 6,7- diF-Q-GH _20- H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

958 6,7-diF-Q-GH _20- H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH

959 6,7-diF-Q-GH _20- H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

960 6,7-diF-Q-GH _20- H 8-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

961 6,7-diF-Q-GH ₂₀ -H 8-C (CH ₃ ) ₂ OH -SC (CH ₃ ) ₂ CH ₂ COOH

962 6,7-diF-Q-GH _20- H 8-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

963 6J-diF-Q-CH ₂₀ -H 8-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

964 6,7-diF-Q-CH ₂₀ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ COOH

965 6,7-diF-Q -CH ₂ 0- H 9-C (CH ₃ ) ₂ OH -SCH ₂ CH ₂ COOH

966 6J- diF-Q -CH ₂ 0- H 9-G (GH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) COOH

967 6,7-diF-Q-GH ₂₀ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

968 6,7-diF-Q-GH ₂₀ -H 9-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₃ ) ₂ COOH

969 6,7-diF-Q-GH _20- H 9-C (CH ₃ ) ₂ OH -SC (CH ₃ ) ₂ CH ₂ COOH

970 6,7-diF-Q-GH _20- H 9-C (CH ₃ ) ₂ OH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

971 6,7-diF-Q-CH ₂ 0-H 9-C (CH ₃ ) ₂ OH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

972 6,7-diCI-Q -OCH ₂ -HH -SCH ₂ COOH

973 6J-diCI-Q -OCH ₂ -HH -SCH ₂ CH ₂ COOH

974 6,7-diCI-Q -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

975 6J-diCI-Q -OCH ₂ -HH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

976 6,7-diCI-Q-OGH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

977 6,7-diCI-Q-OCH ₂ -HH -SC (CH ₃ ) ₂ CH ₂ COOH

978 6,7-diCI-Q -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

979 6,7-diCI-Q-OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

980 6-GI.7-F-Q-OCH ₂ -HH -SCH ₂ COOH

981 6-CIJ-FQ-OCH ₂ -HH -SCH ₂ CH ₂ COOH

982 6-CIJ-FQ -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) COOH

983 6-CI.7-FQ -OCH ₂ -HH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

984 6- CI.7-FQ -OCH ₂ -HH -SCH ₂ C (CH ₃ ) ₂ COOH

985 6-CIJ-FQ -OCH ₂ -HH -SC (CH ₃ ) ₂ CH ₂ COOH

986 6-CI.7-FQ -OCH ₂ -HH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

987 6-CIJ-FQ -OCH ₂ -HH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

988 TQ-I GH ₂ GH2-HH -SCH ₂ COOH

989 TQ-I GHsGHs-HH -SCH ₂ CH (CH ₂ CH ₃ ) COOH

990 TQ one _{GH2GH2 - HH -SC (CH 3)} 2 CH 2 COOH

991 TQ-I GH GH-HH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

996 TQ — GH2GH2-H 7-F -SCH ₂ COOH

997 TQ-I GH ₂ GH2-H 7-F -SCH ₂ CH ₂ COOH

998 TQ-I H 7-F -SCH ₂ CH (CH ₃ ) COOH

999 TQ H uHs— H 7-F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

1000 TQ H2 H2-H7-F -SCH ₂ C (CH ₃ ) ₂ COOH 1001 TQ _GH ₂ GH2-H 7- -F -SC (CH ₃ ) ₂ CH ₂ COOH

1002 TQ — GH ₂ GH2-H 7- -F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

1003 TQ one GH ₂ GH ₂ — H 7- -F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

1004 TQ-I GH2GH2-H 8- -F -SCH ₂ C00H

H 8- -F - SCH₂CH₂COOH 1005 TQ

H 8- -F-SCH ₂ CH ₂ COOH

1 006 TQ i GnsGHs-H 8- -F -SCH ₂ CH (CH ₃ ) COOH

1007 TQ i GH ₂ GH2-H 8- -F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

1008 TQ i Gn ₂ GH2-H 8- -F -SCH ₂ C (CH ₃ ) ₂ COOH

1 009 TQ One H One H 8- -F -SC (CH ₃ ) ₂ CH ₂ COOH

1010 TQ π H— H 8- -F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

101 1 TQ i_ ri vjH— H 8- -F -SCH ₂ C (GH ₂ CH ₂ ) CH ₂ COOH

1012 TQ One H2 Re H2 One H 9- -F -SCH ₂ C00H

1013 TQ — GH H ₂ -H 9- -F -SCH ₂ CH ₂ COOH

1014 TQ —Li HouH-H 9- -F -SCH ₂ CH (CH ₃ ) COOH

1015 TQ _ / HH 9- -F -SCH ₂ CH (CH ₂ CH ₃ ) COOH

1 01 6 TQ one GH H ₂ — H 9- -F -SCH ₂ C (CH ₃ ) ₂ COOH

1017 TQ — / H2 H2-H 9-; F-SC (CH ₃ ) ₂ CH ₂ COOH

1018 TQ uri rl H 9- -F -SCH ₂ CH (CH ₃ ) CH ₂ COOH

1019 TQ リ H Hs-H 9- -F -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

1020 TQ — Re rHouH R — H 7- -CN -SCH ₂ C00H

1021 TQ ^— rlooH "" H 7- -CN -SCH ₂ CH ₂ COOH

H 7- -CN -SCH₂CH(CH₃)COOH1022 TQ

H 7- -CN -SCH ₂ CH (CH ₃ ) COOH

1023 TQ i H 7- -CN -SCH ₂ CH (CH ₂ CH ₃ ) COOH

1024 TQ one rl one H 7- -CN -SCH ₂ C (CH ₃ ) ₂ COOH

1025 TQ 11 H 7- -CN -SC (CH ₃ ) ₂ CH ₂ COOH

1026 TQ one Η;) one H 7- -CN -SCH ₂ CH (CH ₃ ) CH ₂ COOH

1027 TQ — then H;> H2-H 7- -CN -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

1028 TQ one Η;) one H 8- -CN -SCH ₂ C00H

1029 TQ HH ₂ — H 8- -CN -SCH ₂ CH ₂ COOH

1030 TQ H2 H2-H 8- -CN -SCH ₂ CH (CH ₃ ) COOH

1031 TQ One Hs H H--CN -SCH ₂ CH (CH ₂ CH ₃ ) COOH

1032 TQ Whole H2 H2-H8--CN -SCH ₂ C (CH ₃ ) ₂ COOH

1033 TQ-Gl Hs— H 8- -CN -SC (CH ₃ ) ₂ CH ₂ COOH

1034 TQ one H;> re — H 8- -CN -SCH ₂ CH (CH ₃ ) CH ₂ COOH

1035 TQ 1 H ₂ H _2- H 8- CN-SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

1036 TQ ^— G l Ho- H 9- -CN -SCH ₂ C00H

1037 TQ — then H ₂ — H 9- -CN -SCH ₂ CH ₂ COOH

1038 TQ H 9- -CN -SCH ₂ CH (CH ₃ ) COOH

H 9- -CN -SCH₂CH(CH₂CH₃)COOH1039 TQ

H 9- -CN -SCH ₂ CH (CH ₂ CH ₃ ) COOH

1040 TQ One H2 One H 9- -CN -SCH ₂ C (CH ₃ ) ₂ COOH

1041 TQ - G uH one _{H 9- CN -SC (CH 3)} 2 CH 2 COOH

1042 TQ One H One H 9- -CN -SCH ₂ CH (CH ₃ ) CH ₂ COOH

1043 TQ — GH? UH H 9- -CN -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

1044 TQ — then H ₂ -H 7--CF ₃ -SCH ₂ C00H

1045 TQ one GH? Re Ho-H 7--CF ₃ -SCH ₂ CH ₂ COOH

1046 TQ H ₂ — H 7- -CF ₃ -SCH ₂ CH (CH ₃ ) COOH 1047 TO OH CH „-H 7-CF, -SCHoCHfCHoCH COOH

1048 TQ H 7-CF, one SGH G (GH GOOH

 TQ one OH Ρ, Η one H 7-CF -SCfCH ^ CH.GOOH

 \ J% J J TO -OH CM-I H 7- F-OH.OHiOH ^ Η ^ ΩΠΗ

To H 1 1, 1 w M-I H / i Γ Γ1

 ΤΠ Π

1 H ΠΠΠΗ

 1 u τη w -ΠΗ ΠΗ 一 -QOH fifOH) ΠΩΠΗ

1 n 7 τη H

TQ -ΠΗ _Λ Η 一 H 8— G

TO -OH Ο, Η 11-1 H

 1 ΩΒΩ -OH OH-H Q-CF.-SCHnCOOH

 ΤΓ)

 UU I Π H -QfiH OH ΓΪΩΩΗ

 1 Ofi Ku H q-OF -Qrv _ /; Hi, Ρ, Η ιίΌΗ 'ΙΠΠΠΗ

1 TQ one OH ΠΗ one H Q-CF, -SCH.CHfCH.CH COOH

1

 1 TO

 Π H 1

110 uRu τ 1 η w μ 1

τ 1 η 1 ΠΗ ΠΗ1 ΠΗ -QOH)) C ΟΩΗ

 1 \ J J \ J TO -CM ΠΗ 一 Η 1 7-C = CH -SCH.COOH

 TO Η 1 1 -QOH ΠΗ ΟΠΩΗ

 107Ω TO -CM P, H-1 Η 7-C = CH 1 -SCH.CHCCH 'JCOOH

1071 w-H.OH one Η 1 -SCH.CHfCH.CH GOOH

1079 TO Η 1 7-0 = GH -SCH.CfCH ^ COOH

1 u / TO -CM Ρ, Η 一 Η / J— 1-^ P OH) OH ΩΩ

 w Η 7-0 = OH -SCHoCfCHaCH CH.COOH

1 107fi TO -ΠΗ ΠΗ 一 Η -SCHnCOOH

 1077 τη 1 ΠΗ ΠΗ1 μ 1 1

 1107ft TQ μ ft— Π = P.H _cp, u ΠΗΓΡ.Η 1ΠΠΩΗ

1 u / TO Η n -QOwHl, ΠΗ ΟΗ ΟΗ ^ ΟΩΩΗ ι

TQ μ O — \ _ / Π -ςρ _# Η Γ Γ'Η ΠΠΩΗ

1 1 TO μ 11

 TQ one OH Γ'Η 一 -SCHnCHfCH. CH COOH

1083 TQ Η 一 SGH G (GH GH CH GOOH

1084 TQ One CHoCH- Η 9-C≡CH -SCH COOH

Η 9-C三 GH -SCH₂CH₂COOH 1085 TQ

Η 9-C3 GH -SCH ₂ CH ₂ COOH

1086 TQ 1 H Η 9-G3 GH -SCH ₂ CH (CH ₃ ) COOH

1087 TQ | H | H Η 9-G3 GH -SCH ₂ CH (CH, CH ₃ ) COOH

1088 TQ Η 9-C = CH-one SGH C (CH GOOH

1089 TQ — then H2GH2 — Η 9-C = CH -SC (CH ₃ ) ₂ CH ₂ COOH

1090 TQ 1 hsGH-Η 9-G3 GH -SCH ₂ CH (CH ₃ ) CH ₂ COOH

1091 TQ One H HHo-Η 9_C3 GH -SCH ₂ C (CH ₂ CH ₂ ) CH ₂ COOH

1092 TQ — then HsCris Η 7-C (CH ₃ ) ₂ OH -SCH ₂ C00H 1 uyo IU n ₂ Π M ₃ on ₂ Un ₂ UU (

1 U¾ n ₂ Π M3 UVjri

1 Ό Ο 1 U 1 * un ₂ * u Π1 1 Π Π3 sUtl

 I uyo ΤΠ

 Π32

 μΐ

 Pi ¾2 Π 2 1 ~ 1 0 ^ »Π2 ^ * 1 -zPi ΓΙ2 11

Ui

 1 'n n

 u

 I I υυ Π2 Π ο 1 Π O Π

 I I U I ΤΠ 1 ΠΗ ri CM Π 1 u Π 0 1 2 n ri 2 n

 ι r * u

 I I Uo ΤΠ _ρι_

 i Π π π 2 Pi Π Π2 Π3 U Π

 _pu u _

 w Π2 112 Π o π 2 π Ο Π2 1 2 Π

Π2

 11 Uo TO Π π 2 η —COM Π ΠΠΙ Γ-1Ι

11 uy T 1O u one * u I

1 Ί 1 Z 1 u Π Π ₂ Π i 2 "2 Π32

 ■ i 1 u

111 1 u 2 "2 Π y" 3 ί> Π 2 "2 U

 I I I 0 1 — ΠΡΙ-Ι― u

Π Π ₃ O yPl Π

 1 I1I1I / τπ — Π Ι-Ι― u

 Π 7- n unpn Π3 Ο Π2 Π2 Π

 11

 I I O — ΠΡΗ― u Π Π3 Π2 π η

1110 τη one nnw— u Π 7-ΡΠΠΡΗ Π3 l ι

11 n τ 1η -ΠΓϊΗ1 μ / \ j ji \ j \ t 1 is η

 11 9 w one n w-U _ _cpu pufpu ΠΠ UΠVjΗn 1 TO w -ΠΠΗ one H 7— ΠΠΠΡ'Η _cpu u pu) r ΠΩΠΗ

11 Δ Π — now― Π Ο U (J Π _Λ Π £ Π

11 Ί 1 u Uon ₂ Π ti UU M ₃ is M2 π n ₂ I3 uun

11 ά 1 u Γ ^ υ

U n ₂ 1 Π 8 ULJ h ₃ M ₂ 2

 11 Q 1 U ο Ο_οUU Ιr-iΙ

 U "2 Π 3 Π 2 2

 1 I 1 I onu ΤΠ — ΠΡΙ-Ι 一 u

Π Ο U Π ₃ Ο 1 1 '1 π π u

 11 ooo TO -ΠΡ.Η-OH τ 1 η w -ΠΠΗ 一 H _cr; u ΠΗίΤ.Η ΊΠΠΠΗ

1135 TQ -0CH ₂ -H 9-COOCH3 -SCH ₂ CH (CH ₂ CH ₃ ) COOH

1136 TQ-0CH ₂ -H 9-COOCH3 -SCH ₂ C (CH ₃ ) ₂ COOH

1137 TQ -0CH ₂ -H 9-COOCH3 -SC (CH ₃ ) ₂ CH ₂ COOH

1138 TQ -0CH ₂ -H 9-COOCH3 -SCH ₂ CH (CH ₃ ) CH ₂ COOH 1139 TQ -OCH, - H 9- COOCH 3 -SCH 2 C (CH 2 CH 2) CH, COOH In the above Table 1, the abbreviation indicates the following group.

t-Bu, t-butyl group; BO, 2-benzoxazolyl group; BT, 2-benzothiazolyl- group; T et, 1H-tetrazoyl 5-yl group; Me, methyl group I-Pr, isopropyl group; Ph, phenyl group; Py, 2-pyridyl group; Q, quinolin-2-yl group; T, 2-thiazolyl group; TQ, 5,6,7,8 —Tetrahydroquinoline-1-yl In Table 1 above, the numerical value in the general formula (I) indicates a position number.

 More preferred compounds include compounds No. 1, 2, 3, 4, 5, 67, 8, 9, 10,

1 1 1 2,1 3,1,4,15,16,1 718,1 920,2 1,22,23,24,

25 26, 27, 28, 29, 30, 3 1 32, 33 34 3 5 36 37, 38,

39 40, 41, 42, 43, 44, 45 46, 47 48 49 50 59, 60, 61 62, 63, 64, 65, 66, 67 68, 69 70 7 1 72 73, 74,

83 84, 85, 86, 87, 88, 89, 90, 9 92 93 94 95, 96,

97, 98 1 07, 1 08, 109, 1 10, 1 1 1, 1 1 2 1 1 3, 1 14, 1 1 5, 5, 1 16, 1, 17, 1, 11, 19, 1, 20, 1 2 1, 1 2 2, 1 3 1, 1 32, 1 33, 1 34, 1 35, 1 36, 1 37, 138, 1 39, 140, 1 41, 1 42, 143, 144, 1

45, 146, 155, 156, 157, 158, 159, 166, 161, 162, 163, 164, 65, 166, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 187, 188, 189, 190, 191, 192 , 193, 194, 199, 200, 20 1, 202, 2 0 3, 204, 205, 206, 2 1 1 2 1 2, 2 1 3, 2 1 4, 2 1 5, 2 16 , 2 1 7, 2 18, 223, 224,

22 5, 226, 22 7, 2 28, 229, 230, 2 3 1, 2 32, 233, 234, 2.,

35, 236, 23 37, 238, 239, 240, 24 1, 242, 243, 244, 245, 246, 247, 248, 249, 250, 25 1, 260, 26 1, 262, 263,

264, 265, 266, 27, 268, 269, 270, 271, 272, 273, 272, 275, 284, 285, 286, 287, 288, 290, 29 1, 292, 2 9

3, 284, 295, 2 96, 297, 298, 299, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317 , 3 18, 3 19, 320, 3 2 1, 3

22, 323, 3 32, 3 33, 334, 335, 340, 34 1, 342, 343, 34

4, 345, 346, 347, 348, 349, 350, 35 1, 352, 353, 354,

3 55, 3 56, 3 57, 3 58, 359, 360, 361, 362, 363, 364, 365, 366, 366, 368, 369, 370, 371, 372, 3 73, 374, 3 7

5, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 404, 405, 406, 407, 4 1 2 , 4 13, 41, 41, 41, 41, 41, 41, 42, 42 1, 42 '86 '9 86' S 86 '86 '8 8 6' 2 86 'ΐ 86' 086 '6 Z 6' 8 6 'LL 6' 9 Z 6 'SZ 6' 6 '£ Z 6' ZL 6 'S 9 6 '2 9 6' 1 9 6 '0 9 6' 6 S 6 '8 S 6' S 6 '9 9 6' QQ 6 '^ 96' SS 6 'CS 6' ΐS 6 '0 9 6 '6 6 6 38

'8 6' 6 S 6 '8 £ 6' Z £ 6 '9 S 6' SS 6 'S 6' SC 6 'Z £ 6 Ί £ 6 Ό 8 6' 6 2 6 '8 2 6' LZ 6 ' 9 Z 6 'QZ 6' Z 6 '9 I 6' ΐ 6 'ε ΐ 6' Z ΐ 6 ¹ ΐ ΐ 6 '0 ΐ 6' 6 0 6 '8 0 6' 0 6 '9 0 6' S 0 6 '0 6' 8 0 6 'Ζ 0 6

'ΐ 06' 0 06 'ΐ 6 8 '06 8' 6 8 8 '8 88' Ζ 88 '988 8 8', 88 '£ 8 8' Ζ 2 S 'ΐ 8 8' 0 8 8 '6 Ζ 8 '8 Λ 8' Ζ Ζ 8 '9 Ζ 8' Ζ 9 8 '9 9 8' S 9 08 8 '9 8' S 9 8 '2 9 8' 1 9 8 '0 9 8' 6 S 8 '8 S 8 'Ζ S 8' 9 S 8 '2

'S 8' 8 8 '2 S 8' ΐ S 8 Ό S 8 '6 8' 8 8 '6 8 8' 8 8 8 'L £ S' 9 8 8 'S £ 8' £ 2 'SS 8' gg 8 'ΐ S 8 Ό S 8' 6 Ζ 8 '8 2 8' 2 8 '9 Ζ 8' S Ζ 8 '17 2 8' S ΐ 8 '^ ΐ 8' 8 ΐ 8 1 8 'ΐ ΐ 8 Ό ΐ 8 '6 0 8' 8 0 8

'Ζ 08' 9 08 'S 08' 0 8 'S 0 8' 2 08 'ΐ 0 8' 008 Ί 6 Ό 6 Ζ '6 QS

8 I '8 8 Ζ' Ζ 8 Ζ '9 8' 9 2 L 'SL' £ 2 1 'Ζ SL' ΐ 8 Ό Ό 8 Ζ '6 LL' SLI 'Shishishi' 9 IL 'Ζ 9 Ζ' 9 9 Ζ '91' f 9 L '2 91' Ζ 9 I Ί 9 L Ό 9 Ζ '6 S' 8 S 'Ζ 9' 9 9 Ζ 'S 9' S i 'S 9 Ζ' 2 S Ζ ' S ^ 'Ζ

 L 'ΐ ζ' ο f ι '6 ε ζ' 8 ε ζ 'ζ ε' 9 ε '9 ε ζ' ^ ε ζ 'ε ε ζ' 2 ε

L 'ΐ ε Ζ Ό ε Λ' 6 Ζ Ζ '8 Ζ Ζ' L Ζ L '9 Ζ L' ζ Ζ L 'ZL' £ Ζ L 'Ζ Ζ L Ζ Ζ Ζ L' Ο Ζ L '6 ΐ Ζ '8 ΐ Ζ' Ζ ΐ Ζ '9 Ζ Ζ' S ΐ Ζ 'I' 8 ΐ Ζ '2 ΐ Ζ' I ΐ L 'OIL' 6 0 Ζ '8 0 Ζ' 6 6 9 '8 6 9' Ζ 6 9 '9 6 9' 9 6 9 ', 6 9' £ 6

9 'Ζ 6 9' ΐ 6 9 '0 6 9' 6 8 9 '8 8 9' 8 9 '9 8 9' S 8 9 '8 9' 1 9 'VL 9' g 9 'Ζ I 9' Ζ 9 Ό Ζ 9 '6 9 9' 8 9 9 'Ζ 9 9' 9 9 9 'S 9 9' f

9 9 'S 9 9' Ζ 9 9 'ΐ 9 9' 0 9 9 'ΐ 9 9' 0 9 9 '6 key 9' 8 key 9 'L f 9' 9 V ST 9 'S 9' f 9 ' Z 9 'Z t 9 Ί t 9 Ό f 9' 6 8 9 '8 8 9' Z 8 9 '9 £ 9

'LZ 9' 9 Z 9 'Z 9' VZ 9 '8 2 9' ZZ 9 Ί Z 9 Ό Z 9 '6 1 9' 8 ΐ 9 'L ΐ 9' 9 ΐ 9 'SI 9' I 9 'S ΐ 9 'ZI 9' £ 0 9 '2 0 9' ΐ 0 9 '0 0 9' 6 6 S '8 6 9' Z 6 S '9 6 S' S 6 S '^ 6' 8 6 S 'Z 6 9 '1 6 9' 0 6 S '6 8 9

'88 S Ί L 9 Ό L 9 '6 99' 8 9 S '9 S' 9 93 'S 9 S 9 S' S 9 S Οΐ 9 S 'ΐ 9 S' 0 9 S '6 5 9' 8 S 9 'SS' 9 SS '8 S' Z 9 '9 key S' S fg '"s' ε s' s Ί ζ'os' 6 ε s' 8 ε s' z ε s' 9 ε 's ε s '^ ε 9' ε ε 9 'z ε s' zz 'zz ζ Ί z ^l oz' 6 is '8 i 9' ig '9 ΐ 9' SIS 'IS' SIS 'ZI 9' 1 1 9 Ό ΐ S '6 0 S' 8 0 S '6 6 V' 8 6

V Ί 6 '96 '6' key 6 'ζ 6 f' Z 6 f '16 key' 0 6 '6 8,' 8 8 Q

'LS' 9 8 '9 SV' '9 L' f LP '£ I' ZP Ί L f Ό LP '6 9' 8 9 'L 9' 9 9 key '9 9' f 9 f 'Z 9' Z 9 V 'I 9 f' 0 9 key 'ΐ S

 'OS S' 6 f t 'S f' L f '9' 9 t V 'V V' £ f f 'Z f f Ί V

Ό V f '6 £ V' 8 S 'L ζ P' 9 Z 'L Z' 9 Z t '9 Z V' f Z P 'ζ Z' I

 8

90l760 / 00df / X3d 688m OAV 988, 98 9, 990, 991, 992, 993, 994, 995, 996, 997, 998, 999, 1 000, 1 001, 1003, 1004, 1005, 1006, 1007, 1 007, 10009, 10010, 1001, 1,020, 1021, 1022, 1023, 1

024, 1025, 1026, 1027, 1028, 1029, 1030, 1031, 1 032, 1 033, 1 034, 1 035, 1044, 1045, 1 046 , 1 046, 104

8, 1 049, 1 050, 1 05 1, 1052, 1 053, 1 0 54, 1 055, 1 056,

1 057, 1 058, 1 059, 1 068, 1 06 9, 1 070, 1 07 1, 1 072, 1 073, 1 074, 1 07 5, 1 076, 1 077, 1 0 78, 1 079, 1 080, 1 081, 1 082, 1 083, 1 092, 1 093, 1 094, 1 095, 1 096, 1 0 9 7, 1098, 1 099, 1 1 00, 1 1 0 1 , 1102, 1103, 1104, 1105, 1106 or 1107,

 More preferably, compound Nos 1, 2, 3, 4, 5, 6, 7, 8, 9 10 11, 12, 13, 14, 15, 16, 19, 19, 21, 22 , 23, 24, 25 26 27, 28,

29, 30, 31, 32, 35 36 _; 37 38, 39 40 4 1 42 43, 44, 45, 46, 47, 48, 49 50: 59 60, 6 1 62 63 64 65, 66,

83, 84, 85, 86, 8 7 88 89 90, 9 1 92 93 94 95, 96,

97, 98, 107, 108, 109 11 0, 1 11 1, 1 1 2 1 1 3, 1 1 4, 1 1 5, 1 1 6, 1 1 7, 1 1 1 9 and 1 20 , 1 2 1, 1 22, 1 3 1, 1 32, 1 33, 1 34, 1 35, 1 36, 1 37, 1 38, 1 55, 1 56, 1 57, 1 58, 1 59 , 1 60 '1 6 1, 1 62, 1 63, 1 64, 1 65, 1 66, 17 1, 1 72, 1 73, 1 74, 1 75, 1 76, 1 77, 1 78 , 1 79, 180, 1 8 1, 1 82, 1 87, 1 88, 1 89, 1 90, 191, 192, 193, 194, 199, 200, 20 1, 202, 203, 2 04, 205, 206, 2 1 1, 2 1 2, 2 1 3, 2 1 4, 2 2, 3, 224, 2 25, 2 26, 22 7, 228, 229, 230, 23 1, 232, 233, 234, 235, 236, 237, 238, 23 9, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 260 , 261, 262, 263, 264, 26, 5, 266, 267, 268, 269, 270, 27 1, 272, 273, 272, 275,

284, 285, 286, 2 87, 288, 290, 29 1, 2 92, 293, 2 84 '295, 296, 297, 298, 299, 308, 309, 310, 311 , 3 1 2, 3 1 3, 3 14, 3 15 5, 323, 332, 333, 334, 335, 352, 353, 354,

355, 384, 38 5, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 404, 405, 40 6, 407, 4 12, 4, 13 4, 14, 14, 15, 4, 16, 4, 17, 4, 18, 8, 19, 436, 437,

438, 43 9, 440, 44 1, 442, 443, 460, 4 61, 4 62, 46 3, 4 64, 465, 466, 467, 484, 485, 486, 4 8 7, 488, 489 , 4 9

0, 49 1, 508, 509, 5 1 0, 5 1 1, 5 1 2, 5 1 3, 5 14, 5 1 5, 532,

533, 534, 53 5, 536, 537, 538, 53 9, 5, 56, 557, 558, 5 5,9,560,561,562,563,588,589,590,591,592,593,594,595,596,597,598,599,600,601,602,603, 6 1 2, 6 1 3, 6 1 4, 6 1 5, 6 16, 6 17, 6 18, 6 19, 620, 62 1, 62 2, 623, 6 24, 6 2 5 626, 62 7, 6 84, 6 8 5, 686, 687, 68

8, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698,

699, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 72 1, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737,

738, 739, 74 0, 74 1, 742, 743, 752, 753, 754, 755, 7

56, 757, 758, 759, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 800,

801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 824, 825, 826, 82 7, 828, 82 9, 8 30, 83 1, 848, 849, 850, 851, 852, 853, 854, 855,

8 56, 857, 858, 859, 860, 861, 862, 863, 864, 86 5, 8

66, 86 7, 876, 877, 878, 879, 880, 881, 882, 883, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911 , 912, 913, 914, 915, 924, 925, 926, 927, 928, 9

29, 930, 93 1, 93 2, 93 3, 934, 93 5, 93 6, 93 7, 938, 93

9, 9 48, 949, 950, 95 1, 952, 953, 954, 955, 972, 973,

974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 9

84, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994, 995, 996, 997, 998, 999, 1 000, 100 1, 1003, 1004,

1005, 1006, 1007, 1007, 1009, 10110, 1011, 020, 1021, 1022, 1023, 024, 025, 1 026, 1 027, 1 044, 1 0

45, 1 046, 1 046, 1 048, 1 049, 1 050, 1 0 5 1, 1 052, 1 0 5 3, 1 054, 1055, 1056, 1057, 1058, 1 059, 1068, 1 069, 1 070, 1 07 1, 1 072, 1 073, 1 074, 1 075, 1 076, 1 077, 1 0 78, 1 079, 1 080, 1 08 1, 1 082, 1 083, 1 092, 1 093, 1 0

94, 1095, 1096, 1097, 1098 or 1099 compounds,

 Even more preferably, Compound Nos. 1, 2, 3, 4, 5, 6, 7, 8, 10, 10, 11, 12,

13, 14, 15, 15, 16, 21, 22, 23, 26, 27, 28, 31, 31, 32, 35, 36,

37, 38, 39, 40, 41, 42. 43, 44, 45, 46, 47, 48, 49, 50,

59, 60, 61, 62, 63, 64: 65, 66, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 1 07, 1 08, 1 09,

1 1 0, 1 1 1, 1 1 2 1 1 3, 1 1 4, 1 15, 1 16, 1 1 7, 1 1 1 9, 1 20, 1 2 1, 1 22, 1 55 1 56 , 1 57, 1 58, 1 59, 1 60, 1 61, 1 62, 1 6 3, 1 64, 1 65, 1 66, 177, 172, 173, 174, 175, 176, 177, 178, 179, 180, 18 1, 182, 1 87, 1 88, 1 89, 1 90, 1 9 1,

1 92, 193, 194, 199, 200, 201, 202, 203, 204, 205, 206, 22 3, 2 24, 2 25, 226, 227, 228, 22 9, 230, 23 1, 23 2, 23 3, 234, 235, 236, 237, 238, 239, 240, 24 1, 242,

243, 244, 24 5, 246, 24 7, 248, 249, 250, 251, 260, 261, 26 2, 263, 264, 265, 266, 26, 268, 269 , 2 70, 2 7 1, 272, 2 73, 272, 275, 284, 285, 286, 287, 288, 290, 29 1, 292, 293, 284, 295, 296, 2 97, 2 98, 2 99, 32 3, 3 32, 333, 334, 333, 352, 353, 354, 355, 384, 385, 386, 385, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 404, 405, 406, 407, 508, 509, 510, 511, 512, 513, 514 , 5 15, 532, 53 3, 534, 53 5, 536, 53 7, 538, 53 9, 556, 557, 558, 559, 560, 56 1, 562, 563, 724, 725, 726, 727, 728, 729, 730, 73 1, 732, 73 3, 7 • 34, 73 5, 736, 73 7, 738, 739, 740, 74 1, 742, 743, 7 52, 753, 754, 755, 756, 757, 758, 759, 776, 777, 778,

779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 848, 856,

857, 858, 85 9, 860, 86 1, 862, 86 3,864, 86 5,86 6,867, 876, 877, 878, 879, 880, 881, 1, 882, 883, 900 , 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911,

9 1 2, 9 1 3, 9 1 4, 9 1 5, 924, 925, 926, 92 7, 928, 92 9, 9 30, 93 1, 932, 933, 934, 93 5, 936, 93 7 , 938, 93 9, 94

8, 949, 950, 951, 952, 953, 954, 955, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 985, 986 , 987, 988, 989, 990, 991, 992, 993, 994, 995, 996, 997, 998, 999, 1 000, 100 1, 1003, 1004, 1005 , 1006, 1007, 1007, 1009, 1010, 1011, 1020, 1021, 1022, 1023, 1024, 1025, 1 026, 1 027, 1 044, 1 04 5, 1 046, 1 046, 1 048, 1 049, 1 050, 1 0 51, 1 052, 1 053, 1 0 54, 1 0 55, 1 056, 1 057, 1 058, 1 05 9, 1 068, 1 069, 1 0 7 0, 1 07 1, 1072, 1 073, 1074, 1 075, 1076, 1077, 1 078, 1 079, 1080, 1 08 1, 1 082 or 1083

 Particularly preferably,

Compound No. 1; [2-[(E) —2- (6,7-difluoro-2-quinolinyl) ethenyl] 6,11 dihydrobenz [b, e] oxepin-11-yl] oxyacetic acid,

 Compound No. 5; [2-[(E) -2- (6-, 7-difluoro-1-2-quinolinyl) ethenyl] -1,6,1-dihydrodibenz [b, e] oxepin-1 1 1-yl Thioacetic acid,

 Compound N 06; 3-| (2-((E) 1 2— (6,7-difluoro-2-quinolinyl) ethenyl) 1 6 11 1-Dihydrodibenz [b, e] oxepin 1 1— Zyl) propionic acid,

 Compound N 07; 3-| [2-[(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1 6 1 1-Dihydrodibenz [b, e] oxepin 1 1— Yl] thio I 1-2-methylpropionic acid,

 Compound No. 8; 3-| [2-[(E)-2-(6,7-difluoro-2-quinolinyl) ethenyl] -1 6,11-dihydrodibenz [b, e] oxepin 1 1 1 —Yl] thio I —2,2-dimethylpropionic acid,

 Compound N o. 10; 3-1 (2-[(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] 1-6,11-dihydroxybenz [b, e] oxepin-1 1-yl] thio I —2—ethylpropionic acid,

 Compound No. 1 2; 3— | [2 — [(E)-1 2— (6,7-difluoro-2_quinolinyl) ethenyl] −1, 6 1 1 Dihydrodibenz [b, e] oxepin 1 1 _ Yl] thio I —3,3-dimethylpropionic acid,

 Compound N 0.14; I 1-[[2-[(E) 12-(6,7-difluoro-12-quinolinyl) ethenyl] -16,11-dihydroxybenz [b, e] oxepin I 1 1-yl] thiomethyl] cyclopropyl i-acetic acid,

 Compound N 0.16; 2-| [2-[(E)-2-(6,7-difluoro- 1-2-quinolinyl) ethenyl] 1, 6,1 1 -dihydroxybenz [b, e] oxepin 1 1-yl] thio I benzoic acid

 Compound No. 22; [2-[(E) _2— (6,7-difluoro-2-quinolinyl) ethenyl] -6,11-dihydrodibenz [b, e] oxepin-1 1-yl N-methanesulfonylacetic acid amide

 Compound No. 27; 3— [2 — [(E) —2— (6,7-difluoro-1-2-quinolinyl) ethenyl] _6,11—Dihydrodibenz [b, e] oxepin—1 1— Thiol_N-methansulfonylpropionate amide

Compound No. 3 1; 2-| [2-[(E) —2— (6,7-difluoro-2-quinolinyl) ether

1) 6, 1 1—Dihydrodibenz [b, e] oxepin 1 1 1 1] thio I ethanes sulfonic acid

Compound N 0.32; 4— [2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] -6,11-dihydroxybenz [b, e] oxepin 1 1 1 1-yl] butanoic acid compound N 0.36; 3-1 (2-((E) — 2 -— (6,7-difluoro-2-quinolinyl) Ethenyl] 1-fluoro-6,11 dihydrodibenz [b, e] oxepin-11-yl] thio I propionic acid,

 Compound No. 42; | 1-[[2-[(E) -1-2- (6,7-difluoro-12-quinolinyl) ethenyl] -17-fluoro-6,11 dihydrodibenz [b, e] oxepin 1-11-yl] thiomethyl] cyclopropyl I-acetic acid,

 Compound N o. 44; 3— | [2— [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1-8-fluoro-6,11-dihydrodibenz [b, e] oxepin 1 1-yl) thio I propionic acid,

 Compound N o. 60; 3— | [7-Cyan-1-2-((E) — 2— (6,7-difluoro-2-quinolinyl) ethenyl] −1,6,11-Dihydrodibenz [b, e] Oxepin-1)

 Compound No. 84; 3— | [2-[(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] 1-7-trifluoromethyl-6,11-dihydrodibenz [b, e] Oxepin-1 1-yl] thio I propionic acid,

 Compound N 0.108; 3-| [7-ethynyl— 2 _ [(E) — 2— (6,7-difluoro-1-2-quinolinyl) ethenyl] 1 6, 1 1—dihydrodibenz [b, e] oxepin-1 1-yl] thio I propionic acid,

 Compound N 0.15 5; 3— | [2— [(E) — 2— (7-Chloro-6-fluoro-2-quinolinyl) ethenyl] 1-6,11-Dihydrodibenes [b, e] Oxepin] Propionic acid,

 Compound No. 1 59; 3-1 (2-[(E) —2— (7-chloro-6-fluoro-2-quinolinyl) ethenyl] — 7-fluoro-6,11 dihydrodibenz [b, e] Oxepin-1)

 Compound N 0.162; II-[[2-[(E) -2- (7-chloro-1-6-fluoro-1--2-quinolinyl) ethenyl] -17-fluoro-6,11 dihydrodibenz [ b, e] oxepin-11-yl] thiomethyl] cyclopropyl I-acetic acid,

 Compound N 0.17 1; 3— | [2— [(E) —2— (7-Fluoro-2-quinolinyl) ethenyl] 1-6,11-Dihydrodibenz [b, e] oxepin 1 1 1-yl] thio I propionic acid,

 Compound N 0.172; 3— | [2 — [(E) 1 2— (7-fluoro-12-quinolinyl) ether] 1,6,1 1-dihydrodibenz [b, e] oxepin One one one one one] One 2—methyl propionic acid,

 Compound N 0.174; I 1-[[2-[(E) -2- (7-chloro-6-fluoro-2-quinolinyl) ethenyl] -1,6,11-dihydroxybenz [b, e] Oxepin-1 1-yl] thiomethyl] cyclopropyl i-acetic acid,

Compound N 0.23; | 2 — [(E) — 2— (7-chloro-1-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1 1- 1 thioacetic acid, Compound No. 224; 3—i [2 — [(E) —2— (7—chloro-1-2-quinolinyl) ethenyl] -16,11—dihydrodibenz [b, e] oxepin-1 1 1 —Yl] thio i propionic acid,

 Compound N 0.25; 3— | [2-[(E) -1-2- (7-Chloro-2-quinolinyl) ethenyl] -1 6,11-Dihydrodibenz [b, e] oxepin-1 1 1 —Ill! 1-2—methylpropionic acid,

 Compound N 0.227; 11 — [[2-[(E) —2— (7-chloro-1-2-quinolinyl) ethenyl] -1 6,11-dihydroxybenz [b, e] oxepin-1 1 1-yl] thiomethyl] cyclopropyl I-acetic acid,

 Compound No. 229; 3— | [2 — [(E) -I 2_ (5,6,7,8-tetrahydro-2--2-quinolinyl) ethenyl] -1,6,11-Dihydrodibenz [b, e] Oxepin-1)

 Compound No. 230; 3— | [2— ((E) — 2— (5, 6, 7, 8, 8-tetrahydro-2-quinolinyl) ethenyl) 1-6, 11-dihydrodibenz [b, e] Oxepin-1 1-yl] thio I — 2-methylpropionic acid,

 Compound N 0.235; 11— [[2 — [(E) —2— (5,6,7,8-tetrahydro-12-quinolinyl) ethenyl] 1-6,11-dihydrodibenz [b, e] oxepin-l-yl] thiomethyl] cyclopropyl I-acetic acid,

 Compound N 0.352; 3— | [2-[(E) — 2— (6-Fluoro-7-trifluoromethylyl 2-quinolinyl) ethenyl] 1,6,1 1-dihydrobenz [b, e] oxepin 1 1 1-yl] thio I propionic acid,

 Compound N 0.34; 3—1 (3-[(E) — 2— (6,7-difluoro-1-2-quinolinyl) ethenyl] 1 1 0, 1 1—dihydro-1 5 H—dibenz [a, d] Cycloheptene-5-yl] thio I propionic acid,

 Compound No. 385; 3— | [3 -— ((E) —2— (6,7-difluoro-2-quinolinyl) ethenyl) -1-10,11-dihydro-5H—dibenz [a, d] cycloheptene-1 5 —Yl] thio I-12-methylpropionic acid or

 Compound N 0. 404; 3— | [9-[(E) —2— (6,7-difluoro-1-2-quinolinyl) ethenyl] -1,6,1 1-dihydrobenz [b, e] oxepin-1 1 1-yl] Chi! Propionic acid.

The compound represented by the general formula (I) of the present invention can be produced, for example, by the following production methods A, B, C, D, E, F, G or M. Formula A

Process A 2

Formula B

製法 C

Manufacturing method C

HX-Y-CN (I X)

 (I I)

 Or (I I I

Process C 1 (R ² ) ri (R ¹ ) m Process C 2 (R ¹ ) m

 (l b) Process D

工程 D 2

Process D 2

Process E

(I e) Formulation F

Formula G

: x IX) (XX)

RR ² , R ³ , A, B, X, Y, Z, m and And n have the same meanings as described above, and L represents a halogen atom, a C—C ₄ alkylsulfonyloxy group, a fluoroC 1, 1C ,, alkylsulfonyloxy group, or an optionally substituted phenylsulfonyloxy group ( The substituent is a C i -C ₄ alkyl group or a halogen atom, and R ⁴ is a C 1, —C ,, alkyl group or a phenyl group which may be substituted (the substituent is C 1, — A C ₄ alkyl group or a halogen atom), T et represents a 1 H-tetrazo-1-yl 5-yl group, H a 1 represents a halogen atom, and t—B 0 c represents t-butoxycarbonyl. Represents a hydroxyl group.

 Production method A is a method for producing compound (I).

 Step A1 of Production Method A is a step of halogenating or sulfonylating compound (III) to synthesize compound (III).

 The halogenation of the compound (II) is carried out by reacting the compound (II) with a halogenating agent in a solvent or without a solvent (preferably in a solvent).

The solvent used is not inhibit the reaction force is not particularly limited as long as it dissolves a starting substance to a certain extent ⁵ ', for example, methylene chloride, black hole Holm, halogenated hydrocarbons such as carbon tetrachloride or dichloroethane Aromatic hydrocarbons such as benzene and toluene; and aliphatic hydrocarbons such as heptane, hexane and cyclohexane, preferably halogenated hydrocarbons.

 Examples of the halogenating agent include thionyl chloride, thionyl bromide, phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride and the like, and preferably, thionyl chloride or phosphorus oxychloride. The amount of the halogenating agent to be used is generally 1 to 10 moles, preferably 1 to 2 moles, relative to compound (II).

 The reaction is carried out usually at a temperature of from 120 to 100: preferably from 110 to 30 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 5 minutes to 10 hours, preferably 10 minutes to 5 hours.

 The sulfonylation of the compound (Π) is performed by reacting the compound (Π) with a sulfonylating agent in a solvent in the presence of a base.

 The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. For example, the same solvent as used in the halogenation reaction (for example, halogenated hydrocarbons, Aromatic hydrocarbons or aliphatic hydrocarbons), and preferably halogenated hydrocarbons.

Examples of the sulfonylating agent include methanesulfonyl chloride, trifluoromethanesulfonyl chloride, methanesulfonic anhydride, trifluoromethanesulfonic anhydride, benzenesulfonyl chloride, toluenesulfonyl chloride, benzenesulfonyl bromide Or toluenesulfonyl bromide, preferably methanesulfonyl chloride, benzenesulfonyl chloride or toluenesulfonyl chloride. The amount of the sulfonylating agent to be used is generally 1 to 10 moles, preferably 1 to 3 moles, per 1 mole of compound (II). Examples of the base include amines such as triethylamine, triptylamine, diisopropylethylamine, pyridine, picoline, lutidine and 4-dimethylaminopyridine. And preferably triethylamine, diisopropylethylamine or pyridine. The amount of the base to be used is generally 1 to 10 moles, preferably 1 to 2 moles, per 1 mole of the sulfonylating agent.

 The reaction temperature is usually in the range of 110 to 100 ° C, preferably 0 to 30 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 5 minutes to 10 hours, preferably 30 minutes to 5 hours.

 The compound (m) can be separated and purified from the reaction mixture by an ordinary method, but the crude product obtained by concentrating the reaction solution can be used in the next step as it is.

 Step A2 is performed by reacting compound (m) with compound (IV) in a solvent in the presence of a base.

 The amount of compound (IV) to be used is generally 1- to 10-fold, preferably 1- to 5-fold the molar amount of the compound (m).

 The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the substance to some extent. For example, N, N-dimethylformamide, dimethylsulfoxide, N, N-dimethylacetamide or Aprotic polar solvents such as hexamethylphosphoric triamide; halogenated hydrocarbons such as methylene chloride, chloroform or dichloromethane; ketones such as acetone, methyl ethyl ketone or methyl isobutyl ketone; nitritols such as acetonitrile Esters such as ethyl acetate; ethers such as getyl ether, diisopropyl ether, tetrahydrofuran or dioxane; or a mixed solvent thereof, preferably a halogenated hydrocarbon, or an aprotic polar solvent. , Ethers or mixtures thereof Is a Solvent.

 Examples of the base used include alkali metal hydrides such as sodium hydroxide and lithium hydroxide; alkali metal amides such as sodium amide; triethylamine, tributylamine, diisopropylethylamine, and pyridine. And amines such as picoline, lutidine and 4-dimethylaminopyridine; and alkali metal carbonates such as sodium carbonate, potassium carbonate and sodium hydrogencarbonate, preferably amines or alkali metal hydrides. . The amount of the base to be used varies depending on the type of the starting compound, but is usually 1 to 10 times, preferably 1 to 5 times, the molar amount of the compound (IV).

 The reaction is carried out usually at a temperature of 150 to 150 ° C, preferably at a temperature of 110 to 100 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 5 minutes to 10 hours, preferably 30 minutes to 5 hours.

 Step A3 is a step for separately obtaining compound (I), and is suitably employed particularly when X is a sulfur atom. This step is performed by reacting compound (II) with compound (IV) in a solvent in the presence of an acid catalyst.

 The amount of compound (IV) to be used is generally 1 to 5 moles, preferably 1 to 2 moles, per 1 mole of compound (II).

The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting material to some extent. However, for example, halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; alcohols such as methanol, ethanol, propanol, isopropanol and butanol; N, N-dimethylformamide, dimethyl sulfoxide, N Aprotic polar solvents such as N, N-dimethylacetamide or hexamethylphosphate triamide; or ethers such as getylether, diisopropylether, tetrahydrofuran or dioxane; and preferably halogenated hydrocarbons. Kind.

 Examples of the acid catalyst used include: mineral acids such as hydrochloric acid, sulfuric acid, and phosphoric acid; organic acids such as methanesulfonic acid and trifluoroacetic acid; boron trifluoride-ethyl ether complex; zinc chloride; tin tetrachloride; Examples thereof include Lewis acids such as aluminum, and preferred are organic acids or boron trifluoride-ethyl ether complex.

 The amount of the catalyst to be used is generally 0.1 to 50 times, preferably 1 to 10 times, the molar amount of the compound (Π), but when an organic acid is used, a large excess is used also as a solvent. It can also be used for

 The reaction temperature is usually in the range of 10 to 100 ° C, preferably 0 to 30 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 5 minutes to 10 hours, preferably 10 minutes to 5 hours.

In the compound (I), the compound in which Z is a carboxy group (the compound Ic described later) can be directly produced by using the compound (IV) in which Z is a carboxy group, or a compound in which Z is protected. Once the compound (IV), which is a boxy group (preferably the protecting group is a C, —C ₄ alkyl group), is converted to the compound (I), wherein Z is a protected carboxy group, It is also synthesized by hydrolyzing the protecting group under acidic or alkaline conditions by a conventional method.

 In the compound (I), in which Z is a carboxy group, the desired protecting group can be easily introduced by a known method. (See, for example, "Protective Group in Organic Synthesis," 2nd Ed., John Wiley & Sons, W. G. Reenea nd PGH Walt, p. 224.) Production method B is a compound (Ia ).

 The reaction for obtaining the compound (VI) from the compound () or the compound (ΠΙ) and the thiocarboxylic acid (V) in the step B1 is the same as the above-mentioned process except that the thiocarboxylic acid (V) is used instead of the compound (IV). It is performed in the same manner as the method described in Step A2 or Step A3 of A.

 In the step B2, the compound (VI) is hydrolyzed by a conventional method under alkaline conditions to synthesize the compound (W).

 Step B3 is performed by reacting compound (VI) with compound (II) in a solvent in the presence of a base. This reaction is carried out in the same manner as in the method described in the above step A2, except that the compound (W) is used instead of the compound (化合物) and the compound (H) is used instead of the compound (IV).

The amount of compound (II) to be used is generally 1- to 10-fold, preferably 1- to 5-fold the molar amount of the compound (W). Production method c is a method for producing compound (ib). In step c1, the reaction for obtaining compound (X) from compound (π) or compound (m) and compound (K) is carried out in place of compound (IV). The reaction is performed under the same reaction conditions as described in the above-mentioned Method A except that the compound (κ) is used.

 In step C2, compound (Ib) is synthesized by reacting compound (X) with an azide compound in a solvent.

 Examples of the azide compound to be used include, for example, alkali metal azides such as sodium azide, potassium azide or lithium azide; earth metal azides such as calcium azide or magnesium azide; or trimethyl Organic tin azides such as tin azide, tributyltin azide or triphenyltin azide are exemplified. The amount of the azide compound to be used is generally 1- to 10-fold molar amount, preferably 1- to 5-fold molar amount, relative to compound (X). In the reaction, the azide compound may be used alone, or may be a Lewis acid such as aluminum chloride, stannic chloride, zinc chloride, titanium chloride or boron trifluoride-monoethyl ether complex; ammonium chloride or tetrachloride. Ammonium salts such as methylammonium; sulfonic acids such as methanesulfonic acid or ethanesulfonic acid; metal chlorides such as lithium chloride; or amine salts such as triethylamine hydrochloride. Is also good.

 The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. For example, N, N-dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone or N, N — Aprotic polar solvents such as dimethylacetamide; ethers such as getyl ether, tetrahydrofuran, dimethyloxetane, dietoxetane or dioxane; aromatic hydrocarbons such as benzene, toluene or xylene; or hexane Or aliphatic hydrocarbons such as petroleum ether.

 The reaction temperature is usually in the range of 0 to 200 ° (preferably, 50 to 150. The reaction time is usually 1 hour to 72 hours, preferably 3 hours to 48 hours, depending on the reaction temperature and the like. Time.

 Production method D is a method for producing compound (Id) by reacting compound (Ic) with compound (XI) in the presence of a condensing agent (step Dla), or once reacting compound (Ic) After the introduction to the reactive derivative (Step Dlb), the reactive derivative is reacted with the compound (XI) in the presence of a base (Step Dlc).

Examples of the condensing agent used in the step D1a include N, N'-dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDO) , N, N'-carbonyldiimidazole (CD I), azide diphenylphosphoric acid, benzotriazole hexafluorophosphate, 11-yloxy-tris-l- (dimethylamino) phosphonium (BOP), benzoflurophosphate Triazole-1-yloxystris-pyrrolidinophosphonium (PyB0P), hexafluorophosphoric acid 2- (1H-Venztriazole-1-yl) -1,1,3,3-tetramethyl ゥRonium (HBTU) or tetrafluoroboronic acid 2- (1H-benzotriazole-1-yl) -1,1,1,3,3-tetramethylperonium (TBTU) and the like. DCC or Is EDC. The amount of the condensing agent to be used is generally 1 to 5 moles, preferably 1 to 3 moles, relative to compound (Ic).

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Examples thereof include ethers such as getyl ether, tetrahydrofuran, dimethoxetane, diethoxyethane and dioxane; acetonitrile and the like. Aprotic polar solvents such as N, N-dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone or N, N-dimethylacetamide; or methylene chloride, chloroform or dichloroform Halogenated hydrocarbons such as dichloroethane, which can be used alone or as a mixed solvent.

 The reaction temperature is usually in the range of −20 to 100 ° C., preferably 0 to 50 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 30 minutes to 24 hours, preferably 1 hour to 10 hours.

 Examples of the reactive derivative of the compound (Ic) in the step D1b include an acid bromide of the compound (Ic); an acid halide derivative of the compound (Ic) such as an acid chloride; The reactive amide derivative of the compound (Ic) obtained from the compound (Ic) and imidazole, dimethylvirazole, triazole or the like can be mentioned, and an acid halide derivative is preferable. The acid halide of the compound (Ic) can be produced according to a conventional method. For example, the compound (Ic) can be prepared by dissolving the compound (Ic) in a solvent (for example, a halogenated hydrocarbon such as methylene chloride, chloroform or dichloroethane). And the like, and reacting with a halogenating agent (for example, thionyl chloride, thionyl bromide, or phosphorus pentachloride).

 Further, an activated amide derivative of the compound (Ic) can also be produced according to a conventional method. For example, in the case of an imidazole amide of the compound (Ic), the compound (Ic) can be prepared by dissolving the compound (Ic) in a solvent. It can be synthesized by reacting with 1, 1 '_ carbonyldimidazole.

 After formation, the reactive derivative of compound (Ic) can be directly used in the next step Dlb without separation.

 The amount of compound (XI) used in the reaction between the reactive derivative of compound (Ic) and compound (XI) in step Die is generally 1 to 10 times the amount of compound (Ic). Preferably, it is 1 to 5 moles.

 As the base used, for example, triethylamine, triptylamine, diisopropylethylamine, pyridine, picoline, lutidine, 4-dimethylaminopyridine, 1,8-diazabicyclo [5.4.0] pandacene or 1,5-diazabicyclo [5. 4.3.0] Amines such as 7-nonene, and the like, and preferably, triethylamine, triptylamine or diisopropylethylamine. The amount of the base to be used is generally 1- to 10-fold molar amount, preferably 1- to 5-fold molar amount, relative to compound (Ic).

The reaction temperature is generally in the range of 0 to 150 ° C, preferably 10 to 100 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 5 minutes to 48 hours, preferably 30 minutes to 24 hours. Compound (Id) can also be synthesized by a method via compound (II).

 Step D2 is a step of amidating the carboxy group of compound (Ic) to obtain compound (II), and is carried out by appropriately employing a known method. For example, the compound (ΧΠ) can be easily synthesized by reacting the reactive derivative of the compound (I c) with ammonia. Step D3 is performed by reacting compound (ΧΠ) with compound (xm) in a solvent in the presence of a base.

 The amount of compound (xm) to be used is generally 1- to 10-fold, preferably 1- to 5-fold the molar amount of the compound (II).

 The solvent and the base to be used are the same as those described in Step D1, and the reaction is carried out under the same conditions as in Step D1.

 Production method E is a method for producing compound (Ie).

 In the step E1, the reaction for obtaining the compound (XV) from the compound (Π) or the compound (m) and the compound (XIV) is as described above except that the compound (XIV) is used instead of the compound (IV). This is performed in the same manner as described above.

Step E2 is performed by reacting compound (XV) with compound (ΧΠΙ) in a solvent in the presence of a base.

 The amount of compound (xm) to be used is generally 1- to 10-fold, preferably 1- to 5-fold the molar amount of the compound (XV).

 Examples of the solvent to be used include the same solvents as described in the above-mentioned step D1, and are preferably halogenated hydrocarbons or aprotic polar solvents.

 Examples of the base to be used include the same bases as described in the above step D1, and the amount of the base is usually 1 to 10-fold the molar amount of the compound (XIV), preferably 1 to 5 times. It is twice the amount. In this reaction, a large excess of the base can be used also as the solvent. The reaction temperature is usually in the range of −20 to 100 ° C., preferably 0 to 50 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 5 minutes to 10 hours, preferably 30 minutes to 5 hours.

 Preparation F is a separate preparation of compound (Ie).

 The reaction for obtaining the compound (xvm) from the compound (XVI) in the step Fi is performed using a known method known as “Mitsunobu Reaction”, for example, the compound (XVI) And a compound (XVE) in tetrahydrofuran by reacting triphenylphosphine with getyl azodicarboxylate. The amount of triphenyl phosphine to be used is generally 1 to 5 moles, preferably 1 to 5 moles, per 1 mole of compound (XVI). The amount of getyl azodicarboxylate to be used is generally 1 to 1 per compound (XVI).

The molar amount is 10 times, preferably 1 to 5 times.

The reaction temperature is usually in the range of 50 to 80 ° C, preferably -10 to 50 ° C. The reaction time varies depending on the other conditions described above, but is usually 5 minutes to 24 hours, preferably 30 minutes to 10 hours. The method for obtaining the compound (Ie) from the compound (XVm) in the step F2 is performed by a known method, for example, a method of reacting with an organic acid such as trifluoroacetic acid in tetrahydrofuran to deprotect the compound. Will be

 Production method G is a method for producing compound (If).

 Step G1 is a step of producing compound (XX) by triflating compound (XK). Triflatation of the compound (XK) is performed by reacting the compound (XK) with a triflating agent in a solvent in the presence of a base.

 The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Examples thereof include halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride and dichloroethane; Ethers such as tyl ether, tetrahydrofuran, dimethoxetane, diethoxetane or dioxane; aromatic hydrocarbons such as benzene or toluene; or aliphatic hydrocarbons such as heptane, hexane or cyclohexane. Preferably, they are halogenated hydrocarbons or ethers.

 Examples of the triflating agent include trifluoromethanesulfonyl chloride or trifluoromethanesulfonic anhydride, and preferably trifluoromethanesulfonic anhydride. The amount of the triflating agent to be used is generally 1 to 10 moles, preferably 1 to 2 moles, per 1 mole of compound (XK).

 Examples of the base include amines such as triethylamine, triptylamine, diisopropylethylamine, pyridine, picoline, lutidine, and 4-dimethylaminopyridine. Preferably, the base is triethylamine, diisopropylethylamine, or pyridine. is there. The amount of the base to be used is generally 1 to 10 moles, preferably 1 to 2 moles, per 1 mole of the triflating agent.

 The reaction temperature is usually in the range of −20 to 100 ° (preferably, −10 to 50 ° C.) The reaction time varies depending on the reaction temperature and the like, but is usually 5 minutes to 10 hours. Preferably, it is 5 minutes to 5 hours.

 Step G2 comprises reacting compound (XX) with compound (XXI) in an atmosphere of an inert gas such as nitrogen, helium or argon, in the presence of a catalyst (palladium catalyst) and a base in a solvent. Done.

The solvent used is not inhibit the reaction, the force is not particularly limited as long as it dissolves a starting substance to a certain ^extent?, For example, N, N-dimethyl formamidine de, dimethyl sulfoxide, N- methylpyrrolidone or N, Examples thereof include a polar solvent such as N-dimethylacetamide and a solvent such as acetonitrile, and preferably N, N-dimethylformamide.

Examples of the base include amines such as triethylamine, triptylamine, diisopropylethylamine, pyridine, picoline, lutidine, and 4-dimethylaminopyridine, and are preferably triethylamine, diisopropylethylamine or pyridine. . The amount of the base to be used is generally 1- to 10-fold molar amount, preferably 1- to 2-fold molar amount, relative to compound (XX). Instead of amines, a phase transfer catalyst such as tetrabutylammonium chloride or tetrabutylammonium bromide is used in combination with an alkali metal carbonate such as potassium carbonate, sodium carbonate or sodium hydrogencarbonate. You can also.

 Examples of the palladium complex include, for example, palladium acetate, palladium acetate-triphenylphosphine, dichlorobistriphenylphosphine or tetrakistriphenylphosphine, and preferably, palladium acetate-triphenylphosphine or tetrakistriphenyl. Fuphosphine. The amount of the palladium complex to be used is generally 0.01 to 1-fold molar amount, preferably 0.01 to 0.1-fold molar amount, relative to compound (XX).

 Lithium chloride or lithium bromide may coexist in the reaction.

 The reaction temperature is generally in the range of 0 to 150 ° C, preferably 25 to 80 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 30 minutes to 24 hours, preferably 1 hour to 10 hours.

 Production method M is a method for producing compound (la).

Step Ml is carried out by reacting compound (XX XX) with compound (I Va) in a solvent in the presence of a catalyst.

 The amount of compound (I Va) to be used is generally 1- to 5-fold, preferably 1- to 2-fold the molar amount of the compound (XX XX).

 The solvent used is not particularly limited as long as it does not hinder the reaction and dissolves the starting materials to some extent. Examples thereof include halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; and benzene and toluene. Aromatic hydrocarbons can be mentioned, preferably halogenated hydrocarbons.

 As the catalyst to be used, for example, Lewis acids such as boron trifluoride-ethyl ether complex can be used.

 The amount of the catalyst to be used is generally 0.1 to 10 molar times, preferably 1 to 5 molar times, relative to compound (XXXX).

 The reaction temperature is usually in the range of 0 to 100 ° (preferably, 0 to 30 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 5 minutes to 10 hours, preferably 30 minutes to 5 hours. Between.

 In each of the above reactions, the produced target compound is collected from the reaction mixture according to a conventional method. For example, if insolubles are present, they are filtered off as appropriate and then the soot is distilled off, or the solvent is distilled off under reduced pressure, water is added to the residue, and a water-immiscible solvent such as ethyl acetate is added. It can be obtained by extracting with an organic solvent and, if necessary, drying after drying over anhydrous sodium sulfate or the like, and then distilling off the solvent. If necessary, further obtain it by a conventional method, for example, recrystallization, column chromatography, etc. It can be purified.

Further, the compound of the general formula (I) of the present invention can be converted into a pharmacologically acceptable salt by treating with a acid or a base according to a conventional method. For example, an inert solvent (preferably, methyl ether, tetrahydrofuran, dimethoxetane, dietoxetane or dioxa) Ethers such as methanol, ethanol, propanol, isopropanol or butanol; halogenated hydrocarbons such as methylene chloride, chloroform; or water) with a desired acid or base. The desired salt can be obtained by distilling off the solvent or collecting the precipitated crystals by filtration. Also, directly from the reaction mixture of the final reaction step,

It can also be separated as a salt.

 Furthermore, the compounds of the general formula (I) include optical isomers (including diastereomers) based on asymmetric carbons and / or geometric (E, Z) isomers based on unsaturated carbons. For each of these isomers, the corresponding racemic or geometric isomer mixture can be obtained by the usual optical resolution method (fractionated crystallization, optical resolution power, column chromatography, or diastereomer method, etc.) or separation method (recrystallization method, column chromatography, etc.). Can be separated by treating according to For example, when separating an optically active substance, the racemic compound (I) is reacted with an optically active sulfonic acid compound (such as (S) or (R) -camphor-10-sulfonic acid) to form a diastereomer. An optically active compound can be obtained by obtaining one of the monosalts and, if necessary, further purifying the resulting diastereomer salt according to a conventional method. In addition, a desired optical isomer or geometric isomer can also be obtained by performing the above-mentioned reaction using the optically resolved or separated raw material compound.

 Compounds used as starting materials in processes A, B, C, D, E, F, G and M above

(I), (v), (vm), (κ), (χι), (XI), (χιν), (χνι), (χ) and other auxiliary ingredients are all known compounds or It is easily manufactured according to known methods. Compound (II) is produced according to Production method I or J shown below, compound (XXIVa) is produced according to Production method I shown below, compound (XKa) is produced according to production method K shown below, and compound (XXIVa) I) is produced, for example, according to Production method L shown below, and compound (XX XX) is produced according to Production method N shown below. Formula H

製法 I

Formula I

Process I 2

 (XXV) (XXV I

 (XX I V a) Production method J

 (XX I V) Production method K

(XXX III

 (XXXV I) (XXXV I I)

Process 6

製法し

Manufacturing method

 A,

CH _a

 (Reference 1)

 (XX I I I a) (X I)

(Reference 1) J. Org. Chem., 61, 3398 (1996)

(XX XX VI)

 Formula P

工程 P 1 工程 P 2

Process P 1 Process P 2

製法 Q (XXXXV III) (XXXX IX)

Manufacturing method Q

工程 Q 1

Process Q 1

 (XX X X X I I) (XX I X)

In the above formula, R ¹ , R ² , A, B, Ha 1, m and n have the same meanings as described above, and R ⁵ is a hydrogen atom or a group represented by the formula —P (R ^e ), -H a 1

Wherein R ⁶ is a C, 1 C ₄ alkyl group or a phenyl group

And Ac represents an acetyl group, R " ⁷ represents a (^ —C ₄ alkyl group, R ⁸ represents a halogen atom having the same meaning as R ¹ , a nitro group, a cyano group, and C _t having the same meaning as R ¹ one C ₄ alkyl group, Furuoro C of the same meaning as R ^1, -. alkyl group, the same meaning as R ¹ C - C ₄ alkoxy group, Furuoro C of the same meaning as R ^1, - C ₄ alkoxy group, or R ¹ Represents a C! C ₄ alkylthio group having the same meaning as above, r represents an integer of 1 to 4, and when r is 2 or more, R ⁸ may be different; Et represents an ethyl group; THP represents a tetrahydrovinyl group, and TBS represents a t-butyldimethylsilyl group.

 Production method H is a method for producing compound (Π).

Step HI of Production Method H is a method using a compound (xxm, R ⁵ = hydrogen atom) as a raw material (step HI a) or a compound (ΧΧΠΙ), R ⁵ = formula — P (R ^e ) ₃ · H a 1 group ) (Step H1b).

The method using the compound of step HIa (ΧΧΠΚR ⁵ = hydrogen atom) is carried out by reacting the compound (ΧΧΠ) with the compound (xxm, R ⁵ = hydrogen atom) in acetic anhydride. The amount of compound (XXI, hydrogen atom) to be used is generally 1- to 10-fold molar amount, preferably 1- to 5-fold molar amount, relative to compound (II).

 The reaction temperature is usually in the range of 20 to 200 ° C, preferably 50 to 150 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 1 hour to 200 hours, preferably 3 hours to 100 hours.

The method using the compound of step H 1 b (XXD1, R ⁵ = formula _P ⁶ ) ₃ .Ha 1 group) is based on the compound (ΧΧΠ) and the compound (ΧΧΠΙ, = formula—p (R6) ₃ · Ha 1 group) Is carried out in a solvent in the presence of a base. The amount of the compound (XXffl, R ⁵ = formula _P (R ^e ) ₃ 'HaI group) used is usually 1 to 5 times, preferably 1 to 2 times the molar amount of the compound (XXΠ). is there.

The solvent used is not inhibit the reaction, the force is not particularly limited as long as it dissolves a starting substance to a certain extent, such as benzene, aromatic hydrocarbons such as toluene or ^xylene;? Jechi Rue one ether, Jiokisan or Ethers such as tetrahydrofuran; halogenated hydrocarbons such as methylene chloride, chloroform and dichloroethane; and aprotic polar solvents such as N, N-dimethylformamide or dimethylsulfoxide. Aromatic hydrocarbons or ethers.

As the base to be used, for example, alkali metal hydrides such as sodium hydride, lithium hydride or potassium hydride; alkali metal amides such as sodium amide or lithium disopropyl amide; sodium Alkali metal alkoxides such as methoxide, sodium ethoxide or potassium t-butoxide; or alkyllithiums such as methyllithium, butyllithium or t-butyllithium, preferably sodium hydride or lithium hydride. Diisopropylamide, potassium t-butoxide, butyllithium or t-butyllithium. The amount of the base to be used is generally 1 to 3 moles, preferably 1 to 1.5 moles, per mole of the compound (XXffl, R ⁵ = Formula 1 P (R ^e ) 3 · Ha1 group). is there.

 The reaction is carried out usually at a temperature of from 80 to 100 ° C, preferably from -60 to 50 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 10 minutes to 10 hours, preferably 15 minutes to 6 hours.

 The reduction reaction of compound (XXIV) in step H2 to compound (II) is performed using a reducing agent in a solvent.

 Examples of the reducing agent include sodium borohydride, lithium borohydride, sodium cyanoborohydride, lithium aluminum hydride, and the like, and preferably sodium borohydride.

 Solvents used include, for example, alcohols such as methanol, ethanol, propanol, isopropanol and butanol; ethers such as tetrahydrofuran, dioxane or 1,2-dimethoxetane; nitriles such as acetonitrile; N, N Amides such as dimethylformamide, N, N-dimethylacetamide or N-methylpyrrolidone; water; or a mixed solvent thereof, and preferably methanol, ethanol, tetrahydrofuran, N, N-dimethylformamide, N, N-dimethylacetamide or a mixed solvent thereof.

 The reaction temperature is usually in the range of -10 to 150 ° C, preferably 0 to 100 ° C. The reaction time varies depending on other conditions such as the reaction temperature, but is usually from 10 minutes to 10 hours, preferably from 30 minutes to 6 hours.

 Production method I is a method for producing compound (XXIVa).

Step I1 is carried out by reacting compound (XXV) with compound (XXma) in acetic anhydride, except that compound (XXma) is used in place of compound (ΧΧΙΠ, R ⁵ = hydrogen atom). This is performed by the same method as described in the above step H1.

 In step I2, the compound (XXW) is produced by hydrolyzing the compound (XXVI) in a conventional manner under alkaline conditions.

 Step I3 is performed by reacting compound (XXW) with compound (XXK) in a solvent in the presence of a base. The amount of compound (XXK) to be used is generally 1- to 5-fold molar amount, preferably 1-2-fold molar amount, relative to compound (XXW).

The solvent and base used in step I3 are the same as those described in step A2. The same can be mentioned, and the reaction is performed under the same conditions as those described in Step A2.

 Step 14 includes a step of hydrolyzing an ester group of compound (XXI) to obtain a carboxylic acid form (step I4a) and a step of producing a compound (XXIV) by cyclizing the carboxylic acid form (Step I4b) is included.

 The hydrolysis of the ester group of the compound (XXH) in the step 14a can be easily performed according to a conventional method under alkaline or acidic conditions.

 Step I4b is carried out by reacting the carboxylic acid form of the compound (XXII) obtained above in a solvent in the presence of a catalyst (a dehydrating agent).

 The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. For example, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride or dichloroethane; or Nitrobenzene or carbon disulfide power is preferred, and halogenated hydrocarbons are preferred.

 Examples of the catalyst used include: mineral acids such as sulfuric acid, phosphoric acid and polyphosphoric acid; acid anhydrides such as methanesulfonic anhydride and trifluoroacetic anhydride; or boron trifluoride-dimethyl ether complex; Examples thereof include Lewis acids such as aluminum and zinc chloride, and preferred are polyphosphoric acid, methanesulfonic anhydride, trifluoroacetic anhydride, and hydrogen trifluoride-ethyl ether complex. Also, a mixture of trifluoroacetic anhydride and boron trifluoride-diethyl ether complex is suitably used.

 The amount of the catalyst to be used is generally 1- to 10-fold molar amount, preferably 1- to 5-fold molar amount, relative to compound (XXII) or its carboxylic acid form.

 The reaction temperature is generally in the range of 0 to 100 ° C, preferably 0 to 50 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 5 minutes to 24 hours, preferably 30 minutes to 18 hours.

 Preparation J is a separate preparation of compound (XXIV).

 Step J1 is a step of obtaining a compound (XX) by triflating the compound (XXX), and is performed in the same manner as in the step G1 except that the compound (XXX) is used instead of the compound (XK). It is.

 Step J 2 is a step of obtaining a compound (XXIV) by performing a coupling reaction between the compound (XXXI) and the compound (XXI). This reaction is performed by replacing the compound (XXXI) with the compound (XX). The other steps are performed in the same manner as in the step G2.

 Production method K is a method for producing compound (XKa).

 In the step Ki, the compound (xxxm) and the compound () π) are reacted according to a known method, for example, in ethyl acetate in the presence of an acid catalyst such as hydrochloric acid, p-toluenesulfonic acid or pyridinium p-toluenesulfonic acid. It is performed by a method for causing the above.

Step K2 is performed by reacting compound (II) with compound (XXXIV) in a solvent using a base. In this reaction, compound (ΧΧΧΠΙ) is used in place of compound (ΧΧΠ), and compound (XXXIV) is used in place of compound (ΧΧΠΚ R ⁵ = Formula I P (R ^e ). Other used, the compound of step HI (ΧΧΠΙ, R ^e = formula - P ⁶⁾ is carried out in the same manner to obtain the compound (XXIV) with a ₃ 'Ha 1 group).

 The reaction for producing compound (XXXVI) from compound (XXXV) in step K3 is carried out by a known method, for example, deprotection using tetra-n-butylammonium fluoride 1.0M tetrahydrofuran solution in tetrahydrofuran. The reaction is carried out by a method or the like.

 The reaction for producing compound (XXXVE) from compound (XXXVI) in step K4 is carried out by performing a rearrangement reaction in a solvent in the presence of an acid catalyst.

 The solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Examples thereof include alcohols such as methanol, ethanol, propanol and butanol; tetrahydrofuran, dioxane and Organic solvents consisting of ethers such as 1,2-dimethoxetane; nitriles such as acetonitrile; and amides such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methylpyrrolidone. A mixed solvent of one or more kinds of organic solvents and water selected from the group consisting of water, and preferably, a mixture of one or two kinds of organic solvents selected from tetrahydrofuran and an organic solvent composed of N, N-dimethylformamide and water. It is a mixed solvent.

 Examples of the acid catalyst to be used include mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid; and organic acids such as methanesulfonic acid and trifluoroacetic acid. The amount of the catalyst to be used is generally 1- to 100-fold molar amount, preferably 1- to 50-fold molar amount, relative to compound (II).

 The reaction temperature is generally in the range of 0 to 100, preferably 0 to 30 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 5 minutes to 48 hours, preferably 30 minutes to 24 hours.

 Step K5 is performed by reacting compound (XXXW) with compound (XXX¾) in a solvent in the presence of a base. The amount of compound (XXXH) to be used is generally 1- to 10-fold the molar amount, preferably 1- to 5-fold the molar amount of the compound (XXXW).

 As the base used, for example, alkali metal hydrides such as sodium hydride or lithium hydride; alkali metal alkoxides such as sodium methoxide, sodium ethoxide or potassium t-butoxide; methyl lithium or Examples include alkyllithiums such as butyllithium; and metal amides such as sodium amide or lithium disopropylamide, and are preferably metal hydrides.

 The amount of the base to be used is generally 1 to 5 moles, preferably 1 to 2 moles, per 1 mole of compound (XXXII).

The solvent used in step K5 is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent. Examples thereof include aromatic hydrocarbons such as benzene and toluene; tetrahydrofuran, dioxane, and dimethoxane. Ethers such as toxetane or jetoxetane; or aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide or dimethyl sulfoxide; and ethers are preferable. It is. The reaction temperature is usually in the range of 50 ° C to 100 ° C (preferably in the range of 10 ° C to 50 ° C). You.

 The reaction time is usually 15 minutes to 12 hours, preferably 30 minutes to 5 hours.

 Step K6 is carried out by subjecting compound (XXXK) to catalytic reduction with hydrogen in the presence of a catalyst in a solvent.

 The solvent used in step K6 is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Examples thereof include alcohols such as methanol or ethanol; and ethers such as tetrahydrofuran or dioxane. And preferably alcohol frequency.

 Examples of the catalyst used in step K6 include palladium-one carbon, platinum-one carbon, platinum oxide, and rhodium-carbon. In the reaction of Step K6, the hydrogen partial pressure is usually 1 to 10 atm, preferably 1 to 3 atm.

 The reaction temperature is generally in the range of 0 ° C to 100 ° C, preferably 20 ° C to 80 ° C. The reaction time varies depending on the reaction temperature and the like, but is usually 15 minutes to 72 hours, preferably 30 minutes to 48 hours.

 Production method N is a method for producing compound (XX XX).

 Step N1 is a reduction reaction from compound (XXXa) to compound (XXXXI), which is performed using a reducing agent in a solvent. This reaction is carried out in the same manner as in the method for obtaining compound (Π) in step H2.

 Step N2 is carried out according to a known method, for example, by reacting compound (XXXXI) in methanol in the presence of an acid catalyst such as hydrochloric acid, p-toluenesulfonic acid or pyridinium p-toluenesulfonic acid, and the like. Will be

 Step N3 is carried out according to a known method, for example, by reacting compound (II) with a silylating agent in tetrahydrofuran in the presence of a base catalyst such as imidazole and the like. Step N4 is a step of converting a compound (ΧΧΧΧΙΠ) having a halogen atom into a compound (XXXXIV) having an ester group, which is described in "Organic Metal Chemistry (New Experiments, 12)", Maruzen (1975) After the lithiation by lithium-halogen exchange between the alkyl lithium and the organic halide described in (1), (1) carboxylation by reacting with carbon dioxide, followed by treatment with an alkylating agent such as dimethyl sulfate, or ② It is implemented by treating with a carbonate such as dimethyl carbonate.

 The reaction for producing the compound (XX XXV) from the compound (XX XXIV) in Step N5 is carried out by a known method, for example, using a 1.0 M tetrahydrofuran solution of tetra-n-butylammonium fluoride in tetrahydrofuran. It is carried out by a method such as a protection reaction.

Step N6 is carried out by reacting compound (XXXXV) with trifluoromethanesulfonic anhydride in a solvent in the presence of a base, except that compound (ΧΧΧΧΠ) is used in place of compound (XK). The reaction is performed in the same manner as in the method for obtaining the compound (XX) in the step G1. Step N7 is a coupling reaction between compound (XX XXVI) and compound (XX I). This reaction is carried out in a solvent under an inert gas atmosphere using a palladium catalyst. This reaction is Compound (XX) is used in place of compound (XX), except that compound (XX) is used in place of compound (XX).

 Production method 0 is a method for producing compound (XXIV).

 Step 01 is a coupling reaction between compound (XXXXVI1) and compound (XXI). This reaction is carried out in a solvent under an inert gas atmosphere using a palladium catalyst. This reaction was carried out in the same manner as in the step G2 except that the compound (XXXXW) was used in place of the compound (XX) and that the reaction did not involve lithium chloride or lithium bromide. It is performed in the same way as.

 Production method P is a method for providing the compound (xxm) used in step H1 of Production method H. In step P1, the compound (XXXXM) and the <<, /? _ Unsaturated aldehyde are reacted with an acid in a solvent as described in J. Org. Chem., 42, 911 (1977). This is performed using a catalyst.

 In the step P2, as described in JP-A-9-131059, the compound (XXXXK) is reacted with a brominating agent such as N-bromosuccinic acid imide in a solvent, for example, benzoyl peroxide or benzoyl peroxide. , 2'-I-azobis (isobutyronitrile) and the like.

 Step P3 is easily carried out by reacting compound (XXXXX) with trifinylphosphine in a solvent according to a known method.

 Production method Q is a method for producing compound (XXK) used in step I1 of production method I. Compound (ΧΧΧΧΧΠ) is produced by a known method, for example, bromination such as N_bromosuccinimide. The reaction can be carried out by reacting the agent in the presence of a radical initiator such as benzoyl peroxide or 2,2, -azobis (isobutyronitrile).

 Compound (Π), compound (ΧΚ) and compound (XXI) include optical isomers (including diastereomers) based on asymmetric carbons and / or geometric (Ε, Ζ) isomers based on unsaturated carbons. Exists. For each of these isomers, the corresponding racemic or geometric isomer mixture can be prepared by the usual optical resolution method (fractionated crystallization, optical resolution column chromatography or diastereimer method) or separation method (recrystallization method, column chromatography). Can be separated. For example, when separating an optically active compound, the racemic compound (I) is reacted with an optically active sulfonic acid compound (such as (S) or (R) -camphor-1 10-sulfonic acid) to obtain a diamine. An optically active compound can be obtained by obtaining one of the stereoisomers and, if necessary, further purifying the resultant, and then decomposing the obtained diastereomers in a conventional manner.

 Compounds (xxn), (xxm), (xxm a) used as starting materials in Process Η, Process I, Process J, Process K, Process L, Process N, Process 0, Process P and Process Q ), (xxv), (x

(XK), (XXX), (ΧΧΧΠ), (XX XIV), (XXXM), (XXX a), (XXXXVE), (X XXXW), (XXXXX Π) and other auxiliary materials are all known compounds. Or it is easily produced according to known methods. Industrial applicability

The compound of the present invention represented by the formula (I) has a potent leukotriene antagonistic activity, It is extremely useful as an anti-inflammatory and anti-inflammatory drug.

 Dosage forms for that purpose include, for example, oral administration such as tablets, capsules, granules, powders or syrups, or intravenous injections, intramuscular injections, suppositories, inhalants, and aerosols. Parenteral administration with an agent or eye drops. The dosage varies depending on age, body weight, symptoms, dosage form, number of administrations, etc., but usually about 0.1 to 1,000 mg / day for adults is divided into one or several doses. Administer. Example

 Hereinafter, the present invention will be described in more detail with reference to Test Examples and Examples, but the scope of the present invention is not limited thereto.

Test example 1

Leuco Toryen D ₄ receptor binding test

 <Preparation of receptor sample>

Guinea pig lung cell membrane fraction was used as a receptor preparation. Preparation of the membrane fraction was carried out according to the method of Ahn et al. (Eur. J. Pharma col., 127, 153-155 (11986)). The lungs of Hartley male guinea pigs (400-500 g, SLC Japan) were excised and perfused with physiological saline, and then 10 mM PI PES, 10 mM MgCl ₂ , 1 OmM Ca C 1 ₂ Buffer (pH 7.5) was added and homogenized. This was centrifuged at 70,000 X g for 10 minutes to obtain a membrane fraction.

<Roikotoryen D ₄ receptor binding test>

Leukotriene 0 ₄ (LTD ₄₎ receptor binding studies, Aharoni - (Ah ar 0 ny) et al ways (J P ha rma col E xp 1. Th er, 243, 92 1 -... 926 (1 987)). 1 0 mM to receptor preparation 0. 42mg PI PE S, 1 OmM MgC l 2, 1 OmM C a C 1 2 buffer (pH 7. 5) was added, 480 1, _{^{and, [3 H] LTD 4 (}} NE NL Science Products) and a dimethyl sulfoxide solution of the test compound were added in 101 parts, and the mixture was incubated at 25 ° C for 30 minutes. This was filtered through glass fiber filter paper (Watman, GF / C) using Cellstar (Mrand OR 1 M-3 OR). The filter paper was washed with 1 OmM Tris, 100 mM NaC1 buffer (pH 7.5), and 5 ml of liquid scintillator (Nakarai Tesque, Clearsol I) was weighed, and liquid scintillation was performed. Radioactivity was measured using an analyzer (Packard, 200 OCA). When obtaining the dissociation constant of the LTD ₄ (Kd) is ^[3 H] LTD ₄ was used to 0. 03~0 · 5 ηΜ, nonradioactive LTD ₄ was added 1. [ ³ H] LTD ₄ ii 0.2 nM was used to determine the binding inhibition constant (K i) of the suspended compound. Kd and Ki were determined by the method of Bennett et al. (Neurotran Smitter Receptor Binding, 2nded., Editedby H.I.Yamamu raeta 1., p61-89, Raven Press (1 985)). The results are shown in Table 2. The compounds of Table 2 Roikotoryen D ₄ receptor binding test results test compound p K 1 value test compound p K 1 values Example 2 Compound 9.5 Example 26 (b) 9.5

Compound of Example 3 9.8 Compound of Example 32 (b) 9.1

Compound of Example 49.8 Compound of Example 34 (b) 9.2

Compound of Example 5 (b) 9.6 Compound of Example 3 5 (b) 9.4

Compound of Example 7 (b) 9.7 Compound of Example 40 9.1

Compound of Example 12 Compound 9.8 of Example 43 9.9

Compound of Example 13 (b) 9.2 Compound of Example 44 9.7

Compound of Example 14 9.2 Compound of Example 45 9.8

Compound of Example 15 59.8 Compound of Example 5 1 (c) 9.8

Compound of Example 1 9 9.7 Compound of Example 54 (b) 9.9

Compound of Example 23 Compound 9.3 of Example 58

Compound A 9.5 Compound A: 1 1- (2-carboxyethyl) thio-2- (7-chloro-1-6-fluoroquinolin-2-yl) methoxy-1 6,11-dihydroxybenzenes [b, e] Oxepin (see WO 94/1 93445) Test Example 2

Leukotrien D ₄ induced airway stenosis test

 The airway constriction response was measured by the Kontzett and Rossler method (Arc. Ex. Pathol. Pharma ko 1., 1-95, 71-74 (1940)). It was measured with modification. After anesthesia of Hartley male guinea pig (400-500 g, SLC Japan) with pentobarbital (5 Omg / kg, sc), force trachea was introduced into the trachea and a ventilator (Har V) was used. Artificial respiration was performed by Ard, Mo del 683 The airway internal pressure was measured with a differential pressure transducer (Nihon Kohden, TP-603 T) connected to the tracheal force neuron and used as an index of airway stenosis.

LTD ₄ (0.03, 0.06, 0.13, 0.25, 0.5, 1.2 μg / kg, Sigma) was administered at a lower dose through a force neura inserted into the common jugular vein. Intravenous administration was performed at 5 minute intervals to induce an airway stenosis reaction, and the amount of increase in airway pressure was measured. Test compounds were suspended in 5% carboxymethyl cellulose aqueous sodium 0.5 and orally administered one hour before LTD ₄ dosing. Animals fasted for 24 hours prior to administration of test compound. From dose-response curves of LTD ₄ 50% reaction dose determined Me, the dosage of the control group Test I arsenide compound required to cause 2-fold shift the dose-response curve to high dose side of (A (ED _5.): The It was calculated from the following equation.

A ₂ = (amount of compound administered) / | (ED _{50 of} group to which compound was administered) / (ED _{50 of} control group) —II The results are shown in Table 3. Table 3 Results of leukotriene D4-induced airway stenosis test Compound A 2 ng / kg po lhr)

 Compound of Example 2 (b) 0.0017

 Compound of Example 3 0.0036

 Compound of Example 4 0.0037

 Compound of Example 5 (b) 0.0026

 Compound of Example 7 (b) 0.0035

 Compound of Example 12 0.0049

 Example 13 Compound of (b) 0.0078

 Compound of Example 14 0.0044

 Compound of Example 15 0.0008

 Compound of Example 19 9 0.0024

 Example 23 Compound 0.003

 Example 32 Compound (b) 0.0094

 Compound of Example 34 (b) 0.0077

 Compound of Example 35 (b) 0.0066

 0.0088 of the compound of Example 40

 Compound of Example 43 0.0013

 Compound of Example 44 0.005

 Example 5 Compound of 1 (c) 0.0036

 Compound of Example 54 (b) 0.0023

 Compound of Example 58 0.0064

 Compound A 0.016 Compound A: 1 1- (2-carboxyethyl) thio-2- (7-chloro-6-fluoroquinolin-1-yl) methoxy-6,11-dihydrodibenz [b, e Oxepin (see WO 94/193445) Example 1

 (a) [2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin—11-yl] oxyacetic acid Methyl: (Example compound 1

2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1 1 1-hydroxy-1,6 1 1-dihydrodibenes [b, e] oxepin (1.20 g, 2, 99 mmol) was dissolved in 10 ml of tetrahydrofuran, cooled with water at 0 ° C, and triethylamine (0.85 ml, 5.98 mmol) and methanesulfonyl chloride (0.30 ml, 3.89 mmol) were added. The mixture was stirred at room temperature for 3 hours.

After completion of the reaction, the solvent was distilled off under reduced pressure. The obtained residue was dissolved in a mixture of 15 ml of N, N-dimethylformamide and 5 ml of tetrahydrofuran, and methyl glycolate (0.54 g, 5.98 mmol) was added. Then, the mixture was stirred at room temperature overnight.

 Then, water was added to the reaction solution, and the mixture was extracted with a black hole form. The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was subjected to silica gel chromatography (eluent: hexane Z ethyl acetate = 21 (volume ratio)) to obtain 0.38 g of the title compound as a white solid. .

(b) [2-[(E) -1-2- (6,7-Difluoro-2-quinolinyl) ethenyl] -16,11-dihydrodibenz [b, e] oxepin-1-1-yl] oxyacetic acid : (Exemplary compound 1)

 [2-[(E) -1-2- (6,7-difluoro-2-quinolinyl) ethenyl] -1,6,1-dihydroxybenz [b, e] oxepin-1-1-yl] methyl oxyacetate ( 0.38 g, 0.81 mmol) was dissolved in a mixture of 15 ml of methyl alcohol and 5 ml of tetrahydrofuran, a 1N aqueous solution of sodium hydroxide (2.40 ml, 2.40 mmol) was added, and the mixture was stirred at room temperature for 5 hours. .

 After the completion of the reaction, the pH of the reaction solution was adjusted to about 6.5 using a diluted acetic acid aqueous solution, and the solution was concentrated under reduced pressure. Water was added to the residue, and the precipitated solid was collected by filtration. The obtained solid was washed with getyl ether and dried under reduced pressure to obtain 0.26 g of the title compound as a yellow solid.

m.p.; 206-208 ° C

FAB-MS (m / z); 460 (Μ * + 1)

'Eta - Awakening: _{(S.DMSO- d 6); 4.03 (} s, lH), 5.02 (d, J = 12.2Hz, 1H), 5.49 (s, lH), 6.06 (d, J = 12.2Hz, 1H) , 88 (d, J = 8.5 Hz, lH), 7.31-7.50 (m, 4H), 7.65 (dd, J = 8.5, 2.2 Hz, 1H), 7.74 (d, J = 16.4 Hz, 1H), 7.80 ( d, J = 1.9 Hz, lH), 7.80 (d, J = 16.4 Hz, 1H), 7.89 (d, J = 8.80 Hz, 1H), 7.96 (dd, J = 12.0, 8.0 Hz, 1H), 8.02 ( dd, J = 11.2,9.0Hz, lH), 8.34 (d, J = 8.8Hz, 1H),

(c) [2-[(E) -2- (6,7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydroxybenz [b, e] oxepin-1 1-yl] oxyacetic acid Sodium salt

 [2-((E) — 2- (6,7-difluoro-2-quinolinyl) ethenyl] 1,6,11-dihydrodibenz [b, e] oxepin-l-yl] oxyacetic acid (0.27g , 0.58 mmol) was dissolved in a mixture of ml of tetrahydrofuran and 5 ml of methanol, and 0.1 N-aqueous sodium hydroxide solution (5.80 ml, 0.58 mmol) was added, followed by stirring at room temperature for 1 hour. .

 After the completion of the reaction, the reaction solution was concentrated, and the residue was washed with a mixture of ethyl acetate and getyl ether, and dried under reduced pressure to obtain 0.10 g of the title compound as a pale yellow powder.

m.p.; 202-205 ° C

FAB-MS (m / z); 482 (Μ * + 1) Example 2

(a) 3-1 (2-[(E) -2- (7-chloro-6-fluoro-2-quinolinyl) ethenyl] 1-6,1 1-dihydroxybenz [b, e] oxepin-1 1 1- Thio! Propionic acid: (Example Compound 1 55) 2-[(E) 1-2-(7-Chloro-6_fluoro-2-quinolinyl) ethenyl] 1-1-hydroxy_ 6, 1 1-dihydroxybenz [b, e] oxepin (0.77 g, 1.90 fractions) ol) was dissolved in a mixture of 6 ml of trifluoroacetic acid and 40 ml of methylene chloride, and under ice-cooling, 3-mercaptopropionic acid (0.18ral, 2.09 marl) was added, followed by stirring at room temperature for 30 minutes.

 After completion of the reaction, the reaction solution was concentrated, water was added to the residue, and the precipitated solid was collected by filtration. The obtained solid was dissolved in a mixed solution of chloroform: methanol = 4: 1, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was subjected to silica gel chromatography (eluent: toluene / ethyl acetate = 4/1 (volume ratio)), washed with getyl ether, and dried under reduced pressure to obtain 0.22 g of the title compound as a yellow solid.

m.p .; 204-207 ° C

 FAB-MS (m / z); 506 (Μ '+ 1)

 Ή-NMR (δ, DMSO-de); 2.45-2.80 (ra, 4Η), 5.01 (d, J = 12.9Hz, 1H), 5.37 (s, 1H), 6.18 (d, J = 12.9Hz, 1H) , 6.87 (d, J = 8.5 Hz, 1H), 7.35 (d, J = 16. lHz '1H), 7.30-7.50 (m, 4H), 7.56 (dd, J = 8.5, 2.2 Hz, 1H), 7.71 (dJ = 2.2Hz, 1H), 7.77 (d, J = 16.4Hz, 1H), 7.93 (dJ = 8.8Hz, 1H), 7.99 (d, J = 9.8Hz, 1H), 8.19 (d, J = 7.1 Hz, 1H), 8.35 (d, J = 8.8Hz, 1H), 11.50-13.00 (br. S, 1H)

(b) 3-1 (2-[(E) -2- (7-chloro-6-fluoro-2-quinolinyl) ethenyl] 1-6,1 1 dihydrodibenz [b, e] oxepin-1 1-yl Sodium sodium propionate

 3— | [2 — [(E) —2— (7-chloro-6-fluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1 1-yl] thio I. Dissolve propionic acid (0.10 g, 0.20 ol) in a mixture of 10 ml of methanol, 20 ml of chloroform and 5 ml of tetrahydrofuran, and then add 1N aqueous sodium hydroxide solution (0.20 ml, 0.20 ol) at room temperature. ) Was added and the mixture was stirred at room temperature for 30 minutes.

 After completion of the reaction, the reaction solution was concentrated, and the residue was washed with getyl ether and dried under reduced pressure to obtain 0.09 g of the title compound as a slightly yellow solid.

m.p .; 234 ~ 244 ° C (decomposition)

FAB-MS (m / z); 528 (MV1) Example 3

 11 — [[2-((E) —2- (6,7-difluoro-2-quinolinyl) ethenyl) 1 7-fluoro-6,1 1-dihydrodibenz [b, e] oxepin-1 1-yl Thiomethyl] cyclopropyl monoacetic acid, trifluoroacetate: (Trifluoroacetate of Exemplified Compound 42)

2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1-7-fluoro-11-hydroxy-1 6,11 dihydrodibenz [b, e] oxepin (0.20 g, 0.48 was dissolved in a mixture of 1.0 ml of trifluoroacetic acid and 20 ml of methylene chloride, [-(mercaptomethyl) cyclopropyl] acetic acid (0.10 g, 0.68 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was concentrated, water was added to the residue, and the precipitated solid was collected by filtration. The obtained solid was washed with ethyl acetate and dried under reduced pressure to obtain 0.17 g of the title compound as a yellow solid.

m.p .; 174-179 ° C

FAB-MS (m / z); 548 (Μ * + 1)

'Eta - thigh _{(<?, DMS0-d 6)} ; 0.30-0.50 (m, 4H) (2.20-2.40 (m, 2H), 2.58 (d, J = 12.9Hz, IH), 2.81 (d, J = 12.7Hz, IH), 5.31 (d, J = 13.4Hz, lH), 5.31 (s, IH), 6.04 (d, J = 15.9Hz, IH), 6.92 (d, J = 8.5Hz, IH), 7.35 (d, J = 16.6Hz, IH), 7.21-7.38 (m, 3H), 7.61 (d, J = 8.8Hz, IH), 7.68 (s, lH), 7.80 (d, J = 16.4Hz, IH) , 7.91 (d, J = 8.5Hz, lH), 7.97 (dd, J = 12.0, 7.8Hz, IH), 8.04 (dd, J = ll.0, 9.OHz, IH), 8.37 (d, J = 8.9 Hz, 1H), 11.00-13.00 (br. S, IH) The following compounds of Examples 4 to 41 were obtained in the same manner as in Example 2. Example 4

 [2-[(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] -1,6-dihydrobenz [b, e] oxepin-111] sodium thioacetate: ( Exemplified compound 5) Properties: yellow solid.

m.p .; 210-225 ° C

FAB-MS (m / z); 498 (Μ ^÷ +1)

3· 14(d, J=17.8Hz, 1Η)， 3.19(d, J=17.5Hz, IH), 5.01(d, J=12.9Hz, IH), 5.44(s, IH), 6.16(dJ=12.7Hz,lH), 6.87(d, J=8.3Hz, IH), 7.31 (d, J=16.4Hz, IH), 7.35- 7.45(m，4H)， 7.58(dd， J=8.5, 2. OHz, 1H)， 7.68(d， J=2. OHz, IH) , 7.77(d， J=16. lHz， IH), 7.88(d,J=8.6Hz, IH), 7.94(dd， J=ll.9， 7.8Hz， IH)， 8.00(dd, J=ll.0， 9.0Hz， IH)， 8.32(d, J =8.8Hz, IH) 実施例 5

3 ・ 14 (d, J = 17.8Hz, 1Η), 3.19 (d, J = 17.5Hz, IH), 5.01 (d, J = 12.9Hz, IH), 5.44 (s, IH), 6.16 (dJ = 12.7 Hz, lH), 6.87 (d, J = 8.3 Hz, IH), 7.31 (d, J = 16.4 Hz, IH), 7.35-7.45 (m, 4H), 7.58 (dd, J = 8.5, 2. OHz, 1H), 7.68 (d, J = 2. OHz, IH), 7.77 (d, J = 16. LHz, IH), 7.88 (d, J = 8.6 Hz, IH), 7.94 (dd, J = ll.9 , 7.8Hz, IH), 8.00 (dd, J = ll.0, 9.0Hz, IH), 8.32 (d, J = 8.8Hz, IH)

 (a) 3-| [2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] _6,11 dihydrodibenz [b, e] oxepin-1-1-yl] thio 1 Propionic acid: (Exemplified compound 6)

Properties: yellow solid

m.p.; 213-216 ° C

FAB-MS (m / z); 490 (Μ * + 1)

'Η-thigh (S, DMS0_d ₆ ); 2.49-2.72 (m, 4H), 5.02 (d, J = 12.9 Hz, IH), 5.36 (s, lH), 6, 18 (d, J = 12.7 Hz, 1H), 6.87 (d, J = 3.9 Hz, IH), 7.34 (d, J = 16.4 Hz, IH), 7.36-7.47 (m, 4H), 7.57 (dd, J = 8.5, 2.2 Hz, 1H ), 7.71 (d, J = 2.2 Hz, lH), 7.79 (d, J = 16.4 Hz, IH), 7.90 (d, J = 9.0 Hz, 1H), 7.95 (dd, J = 12.0, 7.8 Hz, IH) ), 8.04 (dd, J = 11.2 ₍ 9.0Hz, IH), 8.37 (d, J = 8.5Hz, IH)

(b) 3-i [2-[(E) -2- (6-, 7-difluoro-2-quinolinyl) ether] 1 1 dihydrodibenz [b, e] oxepin-1 1 1-yl] thio i sodium propionate

Properties: reddish brown solid

m.p.; 213-216 ° C

FAB-MS (m / z); 512 (M * + 1) Example 6

 (a) 3-| [2-[(E) -1-2- (6,7-difluoro-2-quinolinyl) ethenyl] -16,11-dihydrodibenz [b, e] oxepin-1 1-yl Thio I —2,2-dimethylpropionic acid: (Exemplary compound 8)

Properties: yellow solid

FAB-MS (m / z); 518 (M ++ 1)

'H-NMRii, DMS0-d _fl ); 1.10 (d, J = 16.6Hz, 6H), 2.56 (d, J = 12.9Hz, IH), 2.85 (d, J = 12.9Hz, IH), 5.02 (d , J = 12.9Hz, IH), 5.23 (s, lH), 6.21 (d, J = 12.7Hz, IH), 6.87 (d, J = 8.5Hz, 1H), 7.33 (d, J = 16.4Hz, IH ), 7.38-7.45 (m, 4H), 7.58 (dd, J = 8.5, 2, 2 Hz, IH), 7.66 (d, J = 2.2 Hz, IH), 7.78 (d, J = 16.4 Hz, IH), 7.88 (d, J = 8.8 Hz, 1H), 7.95 (dd, J = 12.0, 7.8 Hz, IH), 8.02 (dd, J = 9.0, 2.2 Hz, IH), 8.35 (d, J = 8.8 Hz, IH ), 12.43 (br. S, IH)

(b) 3— | [2-[(E) —2— (6,7-difluoro-2-quinolinyl) ether] 1 6 1 1—dihydrodibenz [b, e] oxepin-1 1 1-yl] Thio I —2,2-Natrium sodium pionate

Properties: yellow solid

m.p .; 181-184 ° C

FAB-MS (m / z); 540 (Μ ^÷ +1) Example 7

 (a) 11-[[2-[(E) -2- (6,7-difluoro-2-quinolinyl) ethenyl] -1,6,1 dihydrodibenz [b, e] oxepin-1 11-yl] Thiomethyl] cyclopropyl I acetic acid: (Exemplified compound 14)

Properties: pale yellow solid

m.p .; 170-173 ° C

 FAB-MS (m / z); 530 (M1)

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 3-j [2-[(E)-2-(6,7-difluoro-2-quinolinyl) ethenyl] 1 7-ethynyl-1 6,11-dihydrodibenz [b, e] oxepin 1 1 1 1 Thiol] propionate sodium salt: (sodium salt of Exemplified Compound 108)

Properties: light orange solid

m.p .; 186-189 ° C

FAB-MS (m / z); 535 (M '+ 1)

'H-NMR (5, DMS0 -d 6); 2.09-2.25 (m, 2H), 2.55-2.61 (m, IH), 2.68-2.78 (m, IH), 5.44 (s, IH), 5.45 (d , J = 12.9Hz, lH), 6.15 (d, J = 12.9Hz, IH), 6.87 (d, J = 8.6Hz, 1H), 7.36 (d, J = 16.4Hz, 1H), 7.37 (t, J = 7.6Hz, IH), 7.47-7.52 (m, 2H), 7.56 (dd, J = 8.5, 2.2Hz, IH), 7.73 (d, J = 2.2Hz, IH), 7.78 (d, J = 16.4Hz , IH), 7.89 (d, J = 8.8Hz, IH), 7.96 (dd, J = 12.0, 8.1Hz, IH), 8.04 (dd, J = ll.2Hz, 9.0Hz, 1H), 8.34 (d, (J = 8.6Hz, IH)

 3—l [2 — [(E) —2— (7_chloro-1-6-fluoro-2-quinolinyl) ethenyl] 17-fluoro-1 6,1 1-dihydrodibenz [b, e] oxepin-1 1 1-yl] thio-1 propionic acid: (Exemplified compound 1 59)

Properties: yellow solid

m.p .; 238-241 ° C

FAB-MS (m / z); 524 (M '+ 1)

 'Η-thigh (<J, DMS0-); 2.54-2.76 (m, 4H), 5.31 (dj = 13.Hz, IH), 5.45 (s, lH), 5.99 (d, J = 13.4Hz, IH) , 6.91 (d, J = 8.5 Hz, IH), 7.30 (d, J = 16.4 Hz, IH), 7.24-7.47 (m, 3H), 7.59 (dd, J = 8.5, 2.2 Hz, 1H), 7.72 ( d, J = 1.9Hz, IH), 7.78 (d, J = 16.Hz, IH), 7.93 (d, J = 8.5Hz, IH), 8.00 (d, J = 9.8Hz, IH), 8.19 (d , J = 7.3 Hz, 1H), 8.36 (d, J = 8.8 Hz, IH), 12.32 (br. S, IH)

 I 1-[[2-[(E) —2— (7_chloro-6-fluoro-2-quinolinyl) ethenyl] 1 7-fluoro-6,1 1-dihydrodibenz [b, e] oxepin 1 1— Thiol) cyclopropyl! Acetic acid: (Exemplified compound 1 62)

Properties: yellow solid

m.p .; 237-239 ° C

FAB-MS (m / z); 564 (M '+ 1)

'Η-thigh (S, DMS0-); 0.30-0.50 (m, 4H), 2.23 (dJ = 15.9Hz, IH), 2.31 (d, J = 15.9Hz, IH), 2.58 (d, J = 12.9Hz) , IH), 2.82 (d, J = 12.7Hz, IH), 5.31 (d, J = 13.4Hz, IH), 5.31 (s, lH),

6.04 (d, J = 13.4Hz, lH), 6.91 (d, J = 8.5Hz, IH), 7.35 (d, J = 16.4Hz, IH), 7.21-7.44 (m, 3H), 7.61 (dd, J = 8.5,1.9Hz, IH), 7.68 (d, J = 1.9Hz, IH), 7.80 (d, J = 16.4Hz, IH), 7.94 (d, J = 8.5Hz, IH) , 8.00 (d, J = 9.8Hz, IH), 8.19 (d, J = 7.3Hz, IH), 8.36 (d, J = 8.8Hz, IH), 12.08 (br.s, IH)

 (a) 3— | [2-[(E) — 2— (7-Fluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin I Propionic acid: (Exemplified compound 17 1)

Properties: pale yellow solid

 'H-NMR (δ, DMSO-de); 2.45-2.80 (m, 4H), 5.02 (d, J = 12.7 Hz, IH), 5.37 (s, 1H), 6.19 (d, J = 12.7 Hz, 1H ), 6.87 (d, J = 8.5Hz, IH), 7.30-7.55 (m, 6H), 7.58 (dd, J = 8.5, 2.2Hz, IH), 7.70 (dd, J = 10.3, 2.4Hz, IH) , 7.72 (s, lH), 7.80 (d, J = 15.6 Hz, IH), 7.84 (d, J = 8.5 Hz, IH), 8.04 (dd, J = 9.0, 6.3 Hz, 1H), 8.38 (dJ = 8.8Hz, IH), 1233 (br.s, IH)

(b) 3—1 (2-[(E) —2— (7-fluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1 1-yl] Propionic acid sodium salt Properties: yellow solid

m.p .; 160-163 ° C

FAB-MS (m / z); 494 (M '+ 1) Example 19

 3-i [2-[(E) -1- (7-Fluoro-2-quinolinyl) ethenyl] -1,6,1 1-dihydrobenz [b, e] oxepin-1 1-yl] thio 1 — 2_ (R) -Methylpropionate sodium salt: (Sodium salt of Exemplified Compound 172)

Properties: pale yellow powder

m.p .; 195-205 ° C

 FAB-MS (m / z); 508 (M '+ 1)

'Η-thigh, DMSO- d ₆ ); 0.98-1.03 (m, 3H), 2.15-2.90 (m, 3H), 5.00 (d, J = 12.7Hz, IH), 5.33 (d, J = 8.6, IH ), 6.23 (dd, J = 12.7, 6.1 Hz, lH), 6.85 (d, J = 8.5 Hz, IH), 7.33-7.51 (m, 6H), 7.56 (d, J = 8.6 Hz, lH), 7.69 -7.86 (m, 4H), 8.03 (dd, J = 9.0, 6.6Hz, IH), 8.38 (d, J = 8.5Hz, IH), Example 20

 (a) I 1-[[2-[(E) -2- (7-fluoro-2-quinolinyl) ethenyl] 1, 6,1 1-dihydrodibenz [b, e] oxepin-1 1-yl] Thiomethyl] Cyclopropyl! Acetic acid: (Exemplified Compound 1 74)

Properties: yellow solid

 FAB-MS (ra / z); 512 (M '+ 1).

'H-NMR (δ DMS0- d 6.); 0.30-0.60 (m, 4H), 2 · 23 (d, J = 15.9Ηζ, IH), 2.34 (d, J = 15.9Hz, IH), 2.53 ( d, J = 12.7Hz, IH), 2.81 (d, J = 12.9Hz, lH), 5.02 (d, J = 12.9Hz, IH), 5.23 (s, lH), 6.24 (d, J = 12.7Hz, IH) , 6.87 (d, J = 8.5 Hz, 1H), 7.3 (d, J = 16.1 Hz, IH), 7.30-7.50 (m, 4H), 7.48 (dd, J = 8.5, 2.7 Hz, 1H), 7.59 (dd, J = 8.5,2.0Hz, IH), 7.68 (d, J = 2.2Hz, IH), 7.70 (dd, J = 10.5,2.7Hz, IH), 7.80 (d, J = 16.8Hz, IH ), 7, 84 (d, J = 8.8Hz, 1H), 8.03 (dd, J = 9.0, 6.6Hz, IH), 8.38 (d, J = 8.5Hz, IH), 11.5-12.5 (br.s, IH)

(b) I 1-[[2-[(E) -2- (7-fluoro-2-quinolinyl) ethenyl] 1, 6 1 1-dihydrodibenz [b, e] oxepin _ 11 1-yl] Thiomethyl] cyclopropyl i Sodium acetate ± 1

Properties: yellow solid

m.p; 149-152 ° C

FAB-MS (m / z); 534 (M '+ l) Example 21

 [2 _ [(E) — 2- (7-chloro-2- quinolinyl) ethenyl] 1, 6,11-dihydridobenz [b, e] oxepin-111] thioacetic acid: (exemplified compound 223)

Properties: yellow-red solid ·

m.p .; 22 ° 231 ° C (decomposition)

FAB-MS (m / z); 474 (Μ * + 1)

'Η-thigh (S, DMS0-); 3.25 (s, 2H), 5.04 (d, J = 12.7Hz, IH), 5.40 (s, IH), 6.18 (d, J = 12.7Hz, 1H), 6.91 (d, J = 8.5Hz, 1H), 7.30-7.50 (ra, 5H), 7.62 (dd, J = 8.8, 2. OHz, 2H), 7.68 (d, J = 1.7Hz, IH), 7.88 ( d, J = 16.4Hz, lH), 7.98 (d, J = 8.5Hz, IH), 8.02 (d, J = 2.9Hz, IH) Example 22

 3—) [2-((E)-2-(7—Chloro-2-quinolinyl) ethenyl) 1,6,1 1—Dihydrodibenz [b, e] Oxepin-1 1 1_yl] Chi! Propionic acid: (Exemplified compound 224) Properties: yellow solid

m.p .; 195-198 ° C

FAB-MS (ra / z); 488 (M '+ 1)

'Η-thigh (, DMS0-); 2.45-2.75 (m, 4H), 5.02 (d, J = 12.7 Hz, IH), 5.37 (s, lH), 6.19 (d, J = 12.7 Hz, IH), 6.87 (dJ = 8.5Hz, lH), 7.35 (dJ = 16.4Hz, IH), 7.30-7.50 (m, 4H), 7.58 (dd, J = 8.8, 2.2Hz, 2H), 7.72 (d, J = 2.2 Hz, IH), 7.79 (d, J = 16.4Hz, IH), 7.89 (dJ = 8.8Hz, IH), 7.99 (d, J = 9.OHz, IH), 8.01 (s, lH), 8.38 (d , J = 8.5Hz, 1H), 12.27 (br. S, IH) Example 23

3-| [2— [(E) —2— (7-Chloro-2-quinolinyl) ethenyl) 1,6,1 1-dihydrobenz [b, e] oxepin-1 1 1-yl] thio I —2— (R) —Methylpropion Acid sodium salt: (Sodium salt of Exemplified Compound 225)

Properties: yellow powder

m.p .; 207-217 ° C

FAB-MS (m / z); 524 (M '+ 1)

'Η-thigh (S.DMSO-); 0.97-1.04 (m, 3H), 2.17-2.90 (m, 3H), 4.99 (dd, J = 12.7, 2.69Hz, IH), 5.34 (d, J = 10.0 , IH), 6.23 (dd, J = 12.7, 6.8Hz, IH), 6.84 (d, J = 8.6Hz, IH), 7.33-7.42 (m, 5H), 7.56 (d, J = 5.6Hz, lH) , 7.57 (dd, J = 8.55, 2.2Hz, IH), 7.74-7.82 (ra, 2H), 7.89 (dd, J = 8.7, 1.8Hz, 1H), 7.97-8.02 (m, 2H), 8.34 (d , J = 8.6Hz, IH) Example 24

 II-[[(2-((E) -2-(7-chloro-port -2-2-quinolinyl) ethenyl)] 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1-yl] Thiomethyl Cyclopropyl I acetic acid: (Example compound 227)

Properties: yellow solid

m.p .; 20 to 206 ° C

 FAB-MS (m / z); 528 (M + l)

'.Eta. s Awakening _{(<?, DMS0- d 6);} 0.30-0.60 (m, 4H), 2.22 (d, J = 16.1Hz, IH), 2.33 (. D, J = 16 lHz, IH),

2.53 (d, J = 12.9Hz, lH), 2.80 (d, J = 12.9Hz, IH), 5.02 (d, J = 12.7Hz, IH), 5.23 (s, lH), 6.23 (d, J = 12.7 Hz, IH), 6.87 (d, J = 8.5 Hz, lH), 7.30-7.50 (m, 5H), 7.58 (dd, J = 8.5, 2.2 Hz, IH), 7.59 (dd, J = 8.3, 2.2 Hz , IH), 7.67 (d, J = 2.2Hz, IH), 7.80 (d, J = 16.4Hz, IH), 7.89 (d, J = 8.8Hz, IH), 7.99 (d, J = 8.8Hz, IH ), 8.01 (s, 1H), 8.38 (d, J = 8.5Hz, IH), 12.08 (br.s, IH)

 3-| [2-[(E)-2-(5,6,7,8-tetrahydro-1--2-quinolinyl) ethenyl] 1, 6 1 1 -dihydrodibenz [b, e] oxepin _ 1 1 1 Thiol] propionic acid: (Example compound 229)

Properties: light yellow solid

m.p .; 150-153. C

FAB-MS (m / z); 480 (M ^f + H)

'H-NMR (<J, DMS0-d ₆ ); 1.65-1.95 (ra, 4H), 2.00-2.25 (m, 2H), 2.45- 2.95 (m, 6H), 4.96 (d, J = 12.7 Hz, IH), 5.30 (s, lH), 6.18 (d, J = 12.7 Hz, IH), 6.79 (d, J = 8.5 Hz, IH), 7.ll (d, J = 16.1 Hz, IH), 7.25- 7.55 (m, 8H), 7.60 (d, J = 2.2Hz, IH) Example 26

3-l [2-([(E) -2- (5,6,7,8-tetrahydro-1-2-quinolinyl) ethenyl)] 1,6,1 1 dihydrodibenz [b, e] oxepin-1 1 1- Thio] I — 2— (R) —methyl propionate sodium salt: (Sodium salt of Exemplified Compound 230) 6 z mm%

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(b) 11-[[[2-[(E) -2- (5-fluoro-2-quinolinyl) ethenyl] 1, 6,1 1 1-dihydrodibenz [b, e] oxepin-1 1-yl] thiomethyl Cyclopropyl I acetic acid sodium salt

Properties: yellow solid

m.p.; 142-144 ° C

 FAB-MS (m / z); 534 (M '+ l) Example 3 2

 (a) 3-1 (2-([E) -2- (5,7-difluoro-2-quinolinyl) ethenyl) 1,6,1 1-dihydrodibenz [b, e] oxepin Thio I propionic acid: (exemplified compound 348)

Properties: yellow solid

FAB-MS (m / z); 490 (Μ * + 1)

 'H-NMR (δ, DMSO-de); 2.40-2.80 (m, H), 5.02 (d, J = 12.9 Hz, IH), 5.36 (s, lH), 6.19 (d, J = 12.7 Hz, 1H ), 6.88 (d, J = 8.5 Hz, IH), 7.30-7.50 (m, 5H), 7.52 (tdJ = 10.0, 2.4 Hz, IH), 7.55-7.65 (m, IH), 7.59 (dd, J = 8.5, 2.2Hz, lH), 7.73 (d, J = 2.2Hz, IH), 7.85 (d, J = 16.4Hz, IH), 7.91 (dJ = 8.8Hz, IH), 8.45 (d, J = 8.8Hz , 1H), 12.0-12.5 (br.s, IH)

(b) 3— | [2-[(E) — 2— (5,7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1—dihydrodibenz [b, e] oxepin-1 1 1-yl Chio! Sodium propionate

Properties: pale yellow solid

m.p.; 210-213 ° C

FAB-MS (m / z); 512 (Μ ^÷ +1) Example 3 3

 (a) I 1-[[2-[(E)-2-(5,7-difluoro-2-quinolinyl) ethenyl] 1, 6,1 1 -dihydrodibenz [b, e] oxepin 1 1 1 Thiomethyl] cyclopropyl I-acetic acid: (Exemplified compound 35 1)

Properties: yellow solid

Ή- thigh _{(S, DMS0-d 6)} ; 0.30-0.60 (m, 4H), 2.22 (d, J = 15.9Hz, IH), 2.33 (d, J = 15.9Hz, IH), 2.52 (d, J = 12.9Hz, IH), 2.80 (d, J = 12.9Hz, IH), 5.02 (d, J = 12.7Hz, 1H), 5.23 (s, lH), 6.24 (dJ = 12.7Hz, IH), 6.87 (d, J = 8.5Hz, 1H), 7.36 (d, J = 16.4Hz, IH), 7.30-7.50 (ra, 4H), 7.52 (dd, J = 10.0 , 2.4Hz, lH), 7.61 (dd, J = 8.5, 2.OHz, 2H), 7.69 (d, J = 2.0Hz, IH), 7.85 (d, J = 16.4Hz, IH), 7.92 (d, J = 8.8Hz, lH), 8.45 (d, J = 8.8Hz, IH), 11.5-12.5 (br.s, IH) (b) I 1-[[2− [(E) —2— (5, 7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydroxybenz [b, e] oxepin-11-yl] thiomethyl] cyclopropyl sodium acetate

Properties: yellow solid

m.p.; 149-152 ° C

FAB-MS (m / z); 552 (M ⁴ + l) Example 34

 (a) 3— | [2-[(E)-2-(5,6,7-trifluoro-2-quinolinyl) ethenyl] -1,6 1 1-dihydrodibenz [b, e] oxepin 1 1 1 —Yl] Thio I propionic acid: (Example compound 356)

Properties: yellow solid

FAB-MS (m / z); 508 (M '+ 1)

 'Η -Thigh (<J, DMS0-); 2.45-2.80 (m, 4H), 5.02 (d, J = 12.9Hz, IH), 5.36 (s, IH), 6.19 (d, J = 12.7Hz, 1H ), 6.87 (d, J = 8.5Hz, lH), 7.36 (d, J = 16.4Hz), 7.35-7.50 (m, 4H), 7.58 (dd, J = 8.5, 2.2Hz, IH), 7.72 (d , J = 2.2Hz, IH), 7.84 (d, J = 16.4Hz, IH), 7.87 (ddd, J = ll.7, 7.1, 2.OHz, 1H), 7.97 (d, J = 8.8Hz, lH ), 8.49 (d, J = 8.8Hz, lH), 11.5-13.0 (br.s, IH)

(b) 3— | [2 — [(E) —2— (5,6,7—trifluoro-1-2-quinolinyl) ethenyl] -1,6,1 1—dihydrodibenz [b, e] oxepin-1 1 1 —Yl] Sodium sodium propionate

Properties: pale yellow solid

m.p .; 235-z37. I

FAB-MS (m / z); 530 (M '+ 1) Example 35

 (a) II-CC2-[(E) -2- (5,6,7-trifluoro-2-quinolinyl) ethenyl] 1-6,11-dihydrodibenz [b, e] oxepin 1 1 1 Thiomethyl] cyclopropyl I-acetic acid: (Exemplified compound 359)

Properties: yellow solid

FAB-MS (m / z); 570 (M '+ 1)

'Η-thigh, DMSO- d ₆ ); 0.30-0.60 (ra, 4H), 2.22 (d, J = 15.9Hz, 1H), 2.34 (d, J = 16.1Hz, IH), 2.52 (d, J = 12.5Hz, lH), 2.80 (d, J = 12.7Hz, IH), 5.02 (d, J = 12.7Hz, IH), 5.23 (s, lH), 6.24 (d, J = 12.7Hz, lH), 6.87 (dJ = 8.5Hz, lH), 7.36 (d, J = 16.4Hz, IH), 7.30-7.50 (m, 4H), 7.60 (dd, J = 8.5,2.0Hz, 2H), 7.68 (d, J = 1.7 Hz, IH), 7.84 (d, J = 16.4 Hz, 1H), 7.80-7.95 (m, IH), 7.98 (d, J = 9.0 Hz, IH), 8.49 (d, J = 8.8Hz'lH), 12. Kbr.s, IH) (b)! 1— [[[2 [[(E) —2— (5,6,7-trifluoro-2-quinolinyl) ethenyl] 1,6-dihydroxybenzenes [b, e] oxepin-11-yl] thiomethyl] cyclopropyl! Sodium acetate

Properties: yellow solid

m.p .; 195-198 ° C

FAB-MS (m / z); 570 (M '+ 1) Example 36

 (a) 3— | [2-[(E) -1-2- (5-Fluoro-2-benzothiazolyl) ethenyl] -1-6,11 dihydrodibenz [b, e] oxepin—11-1-yl] thio I Propionic acid: (exemplified compound 364)

Properties: yellow solid

FAB-MS (m / z); 478 (Μ '+ 1)

'H-NMR (δ, DMS0 -d 6); 2.45-2.80 (m, 4H), 5.03 (d, J = 12.9Hz, IH), 5.32 (s, lH), 6.20 (d, J = 12.7Hz, 1H), 6.87 (d, J = 8.5 Hz, lH), 7.33 (td, J = 9.0, 2. Hz, IH), 7.35-7.50 (m, 4H), 7.48 (d, J = 16. LHz, IH ), 7.62 (d, J = 16.4Hz, IH), 7.64 (dd, J = 8.5, 2.2Hz, IH), 7.75 (d, J = 2.2Hz, IH), 7.79 (dd, J = 10.0, 2.4Hz) , IH), 8.13 (dd, J = 9.0,5.4Hz, IH), 12.31 (br.s, IH)

(b) 3-1 (2-[(E) -2- (5-fluoro-2-benzothiazolyl) ethenyl] 1,6 1 1-dihydrodibenz [b, e] oxepin-1 1-yl] Chio i sodium propionate

Properties: light yellow solid

m.p.;> 300 ° C

 FAB-MS (m / z); 500 (M '+ 1) ■ Example 3 7

 (a) 11 — [[2-((E) —2— (5-Fluoro-2-benzothiazolyl) ethenyl] -1,6,11-dihydrobenz [b, e] oxepin-111] thiomethyl Cyclopropyl I-acetic acid: (Exemplified compound 36 7)

Properties: yellow solid

FAB-MS (m / z); 518 (M '+ 1)

'.Eta. Hokusatsu _{(S, DMS0- d 6);} 0.30-0.60 (m, 4H), 2.22 (d, J = 16.1Hz, IH), 2.34 (d, J = 15.9Hz, IH), 2.53 (dJ = 12.7Hz, lH), 2.80 (d, J = 12.9Hz, IH), 5.03 (d, J = 12.7Hz, IH), 5.19 (s, lH), 6.25 (d, J = 12.5Hz, lH), 6.87 (d, J = 8.5Hz, lH), 7.10-7.50 (m, 5H), 7.47 (d, J = 16.lHz, IH), 7.63 (d, J = 15.9Hz , IH), 7.64 (dd, J = 8.8, 2.2Hz, IH), 7.72 (d, J = 2.2Hz, IH), 7.79 (dd, J = 10.0, .4Hz, IH), 8.12 (dd, J = 9.0, 5.4Hz, IH), 11.5-12.5 (br.s, IH) (b)! 1-[[2-[(E) -2- (5-Fluoro-2-benzothiazolyl) ethenyl] -1,6,11-dihydrodibenz [b, e] oxepin-11-yl] thiomethyl] cyclopropyl I sodium acetate

Properties: yellow solid

in. p .; 155 to 157 ° C

FAB-MS (m / z); 540 (Μ ⁺ +1) Example 38

 (a) 3— | [2 — [(E) —2— (5_fluoro-2-benzobenzoxazolyl) ethenyl] —6,11—dihydrodibenz [b, e] oxepin 1 1— Thiol] propionic acid: (Example compound 372)

Properties; light brown solid

FAB-MS (m / z); 462 (M '+ 1)

'Η-thigh (, DMS0- d ₆ ): 2.45-2.75 (m, 4H), 5.03 (d, J = 12.7Hz, IH), 5.32 (s, IH), 6.20 (d, J = 13.2Hz, IH ), 6.88 (d, J = 8.3Hz, IH), 7.17 (d, J = 16.1Hz, IH), 7.25 (dddJ = 9.8, 8.8, 2.4Hz, IH), 7.35-7.50 (ra, 4H), 7.59 (dd, J = 8.8, 2.9Hz, IH), 7.66 (dd, J = 8.8, 2.0Hz, IH), 7.74 (dd, J = 8.8, 4, 4Hz, 1H), 7.76 (d, J = 16.6Hz , IH), 7.78 (d, J = 2.4Hz, IH), 12.0-13.0 (br.s, IH)

(b) 3— | [2— [(E) — 2— (5_fluoro-2-benzoxazolyl) ethenyl] 1, 6, 1 1—dihydrodibenz [b, e] oxepin 1 1— Thiol) sodium propionate

Properties; brown solid

m.p .; 247-25 (TC

FAB-MS (ra / z); 484 (Μ * + 1) Example 39

 (a) 3— | [2-[(E) —2— (6-Isopropyl-5-methyl-1-pyridyl) ethenyl] -16,11—Dihydrodibenz [b, e] oxepin-1 1-yl] Chi! Propionic acid: (Exemplified compound 380)

Properties: yellow solid

FAB-MS (m / z); 460 (M ++ 1)

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ΐ '9'Η-thigh, DMS0_d ₆ ); 1.25 (d, J = 6.6 Hz, 6H), 2.27 (s, 3H), 2.44-2.68 (m, 4H), 3.20-3.35 (m, IH), 4.98 (d, J = 12.9Hz, lH), 5.36 (s, lH), 6.17 (dJ = 12.7Hz, IH), 7.10 (d, J = 15.9Hz, IH), 7.24 (d, ΐ (ΠΠ) ^ 1 ^ (Ι ⁰ strokes 617 '3θ · ΐ)? ! Ψ [3 'q] ^. ^ Π ^ 1-ΐ ΐ' 9—4

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 96

90l760 / 00df / X3d 688m OAV And 3 ml of trifluoroacetic acid, and dissolved in 1- (mercaptomethyl) cyclopropane ethyl ether rubonate (0.80 g, 4.98ramol), followed by stirring at room temperature for 1 hour.

 After completion of the reaction, the reaction solution was concentrated, water was added to the residue, the pH was adjusted to about 6.5 with sodium hydrogen carbonate, and the mixture was extracted with chloroform. The organic layer is washed with water, dried over anhydrous sodium sulfate, concentrated, and then subjected to silica gel chromatography (eluent: hexane ethyl acetate = 21 (volume ratio)) to obtain 1.30 g of the title compound as a pale yellow viscous oil. Was.

EI-MS (m / z); 543 (Μ '), CI-MS (m / z); 544 (M' + 1)

(b) 1 l [2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1-6,1 1—dihydrodibenz [b, e] oxepin — 1 1—yl Thiomethyl! Cyclopropane carboxylic acid: (Exemplary compound 9)

 1-1- | [2-[(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1-6,1

I-Dihydroxybenz [b, e] oxepin-1-1-yl] Thiomethyl I Cyclopropane power Ethyl rubonate (1.3 g, 2.4 x 01) dissolved in a mixture of 20 ml of methanol and 10 ml of tetrahydrofuran Then, a 1 N aqueous solution of sodium hydroxide (7.2 ml, 7.2 ol) was added, and the mixture was stirred at room temperature for 15 hours. After the completion of the reaction, the pH of the reaction solution was adjusted to about 6.5 using a dilute acetic acid aqueous solution, and the solution was concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent: ethyl hexanoacetate = 1/1 (volume ratio)) to obtain 0.39 g of the title compound as a pale yellow solid.

FAB-MS (m / z); 516 (M '+ 1)

'Η -Hidden (, DMS0-; 0.53-0.58 (m, IH), 0.82-0.87 (m, IH), 1.02-1.09 (m, IH), 2.60 (d, J =

13.5Hz, IH), 2.98 (d, J = 13.ΙΗζ, ΙΗ), 5.02 (d, J = 12.7Hz, IH), 5.33 (s, lH), 6.20 (d, J = 12.7Hz, IH), 6.87 (d, J = 8.5 Hz, IH), 7.30-7.47 (m, 5H), 7.58 (dd, J = 8.5, 2.2Ηζ, .1Η), 7.67 (d, J = 2.2 Hz, IH), 7.78 ( d, J = 16.3Hz, lH), 7.90 (d, J = 8.79Hz, IH), 7.95 (dd, J = 12.0, 8.06Hz, IH), 8.03 (dd, J = ll.0, 8.8Hz, lH ), 8.34 (d, J = 8.8Hz, IH), 12.4 (br.s, IH)

(c) 1—l [2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl]

I I—Dihydrodibenz [b, e] oxepin-1-1-yl] Thiomethyl i Cyclopropane Carboxylic acid sodium salt

 1— | [2-[(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1-6,1 1-dihydrodibenz [b, e] oxepin-1 1 1-yl] thiomethyl i Cyclopropane force Dissolve rubonic acid (0.39 g, 0.76 mmol) in a mixture of 15 ml of tetrahydrofuran and 5 ml of methanol, add 0.5 N aqueous sodium hydroxide solution (1.52 ml, 0.76 mmol), and add 2 hours at room temperature. Stirred. After completion of the reaction, the reaction solution was concentrated, the residue was washed with getyl ether, and dried under reduced pressure to obtain 0.35 g of the title compound as a slightly yellow powder.

m.p .; 175-185 ° C

FAB-MS (M / Z); 538 (M '+ 1) The following compounds of Examples 43 to 45 were obtained in the same manner as in Example 42. Example 43

 3— | [2-((E) -2— (6,7-difluoro-2-quinolinyl) ethenyl) 1,6,1 1—dihydrodibenz [b, e] oxepin-1 1 1-yl] _2— (S) —Methyl phthalic acid sodium salt: (Sodium salt of Exemplified Compound 7)

Properties: ocher powder

m. p .; 193-216 ° C

FAB-MS (m / z); 526 (M * + l)

'H-NMR (5, DMS0-d ₆ ); 0.95-1.00 (m, 3H), 2.14-2.89 (m, 3H), 4.98 (dd, J = 12.5, 2.9 Hz, IH),

5.34 (d, J = 13.7Hz, lH), 6.20 (dd, J = 12.3, 10.2Hz, IH), 6.83 (dd, J = 8.5, 1.22Hz, IH), 7.33-7.41 (m, 5H), 7.53 (dd, J = 8.5, 2.2Hz, lH), 7.75 (s ,, lH), 7.78 (d, J = 16.1Hz, IH), 7.89 (dd, J = 8.5, 2.6Hz, lH), 7.97 (dd, J = 12.0, 8.3Hz, IH), 8.03 (dd, J = ll.0, 8.8Hz, IH), 8.35 (d, J = 8.8Hz, IH) Example 44

 3— | [2-((E) -2— (6,7-Difluoro-2-quinolinyl) ethenyl) 1,6,1 1-dihydrobenz [b, e] oxepin-1 1 1-yl] thio I _2 — (R) — Methyl sodium salt of pionic acid: (Sodium salt of Exemplified Compound 7)

Properties: ocher powder

m.p .; 196-220 ° C

FAB-MS (m / z); 526 (Μ ^÷ +1)

'Η-thigh (3' DMSO-d ₆ ); 0.96-1.01 (m, 3H), 2.20- 2.89 (m, 3H), 4.98 (dd, J = 12.7, 2.7Hz, IH), 5.34 (d, J = 11.7Hz, 1H), 6.21 (dd, J = 12.5, 8.3Hz, IH), 6.83 (d, J = 8.8Hz, IH), 7.33-7.44 (m, 5H), 7.46 (s, lH), 7.55 (d, J = 8.5Hz, 1H), 7.77 (d, J = 16.1, IH), 7.89 (d, J = 8.5Hz, IH), 7.97 (dd, J = 12.0, 8.1Hz, IH), 8.03 ( dd, J = 11.0,8.8Hz, IH), 8.34 (d, J = 8.8Hz, IH)

 3-| [2-((E) —2— (6,7-difluoro-2-quinolinyl) ethenyl) 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1 1-yl] —2-Ethylpropionic acid sodium salt: (Sodium salt of Exemplified Compound 10)

Properties: pale yellow powder

m.p .; 209-218 ° C

FAB-MS (m / z); 540 (Μ '+ 1)

'Η-gut (S, DMS0- d ₆ ); 0.78 (t, 3H), 1.41 (m, 2H), 2.06 (m, IH), 2.54-2.63 (m, 2H), 4.97 (d, J = 12.7 Hz, IH), 5.31 (s, 1H), 6.22 (d, J = 12.5Hz, IH), 6.83 (d, J = 8.5Hz, IH), 7.33-7.41 (m, 5H), 7.54 (d, J = 8.5Hz, lH), 7.77 (d, J = 16.4Hz, IH), 7.78 (d, J = 2.2Hz, IH), 7.90 (d, J = 8.8Hz, IH), 7.99 (dd, J = 12.45 , 7.57Hz, IH), 8.03 (dd, J = ll.2, 9.0Hz, IH), 8.35 (d, J = 8.8Hz, IH) Example 46

 (a) 3-[2-[(E)-2-(6, 7-difluoro-1- quinolinyl) ethenyl] 1, 6-1 dihydrodibenz [b, e] oxepin-1 1 -yl] Thio-N-trifluoromethansulfonylpropionic acid amide: (Exemplary compound 28)

 3-[2-[(E) -2-(6,7-difluoro-2-quinolinyl) ethenyl] 1, 6,1 1 -dihydrodibenz [b, e] oxepin-1 1 1 1] thiopropionic acid (0.54 g, 1. lramol) and trifluoromethanesulfonamide (0.24 g, 1.6 mmol) were dissolved in 20 ml of tetrahydrofuran, and dimethylaminopyridine (0.13 g, 1. lmraol) was added. (Aminopropyl) force rubodimide hydrochloride (0.34 g, 1.8 parts 01) was added, and the mixture was stirred at room temperature for 23 hours.

 After completion of the reaction, water was added to the reaction solution, extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: ethyl acetate / hexane = 1 / l (volume ratio)) to obtain 0.30 g of the title compound as a yellow solid.

m.p .; 152-156. C

FAB-MS (ra / z); 621 (M l)

! H-Hidden (<J, DMS0_d ₆ ); 2.35- 2.70 (m, 4H), 5.00 (d, J = 12.7 Hz, IH), 5.35 (s, lH), 6.18 (d, J = 12.7 Hz, 1H ), 6.85 (d, J = 8.6 Hz, lH), 7, 35 (d, J = 16.3 Hz, IH), 7.35-7.46 (m, 4H), 7.56 (dd, J = 8.6, 2.2 Hz, 1H) , 7.72 (d, J = 2.2 Hz, IH), 7.78 (d, J = 16.4 Hz, IH), 7.89 (d, J = 8.8 Hz, IH), 7.95 (dd, J = 12.0, 8.2 Hz, lH) , 8.02 (ddJ = 11.0, 9.03Hz, lH), 8.35 (d, J = 8.8Hz, IH)

(b) 3— [2 — [(E) -2- (6-, 7-difluoro-1-2-quinolinyl) ethenyl] 1,6,1 1-dihydrobenz [b, e] oxepin-1 1-yl] Thio N-trifluoromethanesulfonylpropionate amide hydrochloride

 3— [2 — [(E) 1 2— (6,7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1 1-yl] —Sodium trifluoromethanesulfonylpropionate amide (0.12 g, 0.19 mmol) was dissolved in 2 ml of tetrahydrofuran, 1 N hydrochloric acid (0.20 ml, 0.20 mmol) was added, and the mixture was stirred at room temperature for 10 minutes. The resulting precipitate was further diluted with distilled water, and the resulting precipitate was collected by filtration. The obtained solid was washed with distilled water and dried under reduced pressure to obtain 0.10 g of the title compound as a yellow solid.

m.p .; 234 ~ 238 ° C

 FAB-MS (ra / z); 621 (Μ * + 1)

'H-NMR («J, DMS0-d ₆ ); 2.44-2.67 (m, 4H), 5.02 (d, J = 12.7Hz, IH), 5.36 (s, lH), 6.18 (d, J = 12.7Hz , 1H), 6.89 (d, J = 8.5 Hz, IH), 7.35 (d, J = 16. IHz, IH), 7.36 (m, 4H), 7.58 (dd, J = 8.5, 2.2 Hz, IH), 7.74 (d, J = 2.2Hz, IH), 7.90 (d, J = 16,1Hz, IH), 7.99 (dd, J = 11.5,7.6Hz, IH), 8.04 (d, J = 9.3Hz, IH) , 8.13 (ddJ = 11.0, 8.8Hz, 1H), 8.52 (d, J = 8.8Hz, IH) (a) [2-[(E)-2-(6,7-difluoro-2-quinolinyl) ethenyl] 1, 6 1 1 dihydrodibenz [b, e] oxepin 1 1 1 -yl] Thio N— Methanesulfonyl acetic acid amide: (Exemplified compound 22)

 [2-[(E) -1-2- (6,7-difluoro-2-quinolinyl) ethenyl] -1,6-dihydrobenzenes [b, e] oxepin-1-1-yl] thioacetic acid (0.66 g, 1.33 rec. ol) and trifluoromethanesulfonamide (0.20 g, 2.10 mmol) are dissolved in 20 ml of tetrahydrofuran. Carbodiimid hydrochloride (0.37 g, 1.93 fractions) was added, and the mixture was stirred at room temperature for 1.5 hours.

 After completion of the reaction, add water to the reaction solution, adjust the pH to about 5.0 with 1 N hydrochloric acid, extract with ethyl acetate, wash the organic layer with saturated aqueous sodium chloride solution, and dry over anhydrous sodium sulfate. did. The solvent was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: hexane / ethyl acetate = 2Z3 (volume ratio)) to obtain 0.23 g of the title compound as a yellow solid.

m.p .; 228-234 ° C (decomposition)

FAB-MS (m / z); 553 (M ++ 1)

'H-NMR (5, DMS0-d ₆ ); 3.25 (s, 3H), 3.30-3.39 (m, 2H), 5.04 (d, J = 12.9Hz, 1H), 5.37 (s, lH), 6.16 ( d, J = 12.9Hz, lH), 6.90 (d, J = 8.3Hz, 1H), 7.3 (d, J = 16.1Hz, 1H), 7.37-7.48 (m, 4H), 7.61 (dd, J = 8.6 ₍ 2.0Hz, 1H), 7.64 (d, J = 2.0Hz, 1H), 7.78 (d, J = 16.4Hz, 1H), 7.87 (d, J = 8.5Hz, 1H), 7.96 (dd ₍ J = 12.0,7.8Hz, 1H), 8.02 (dd, J = 11.0,9.0Hz, 1H), 8.35 (d, J = 8.6Hz, 1H), 11.93 (br.s, 1H)

(b) [2 — ((E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1 1-yl] —Methanesulfonylacetic acid amide sodium salt

 [2-[(E) — 2- (6,7-difluoro-2-quinolinyl) ethenyl] -6,11-dihydrodibenz [b, e] oxepin- 1 1-yl] After methanesulfonylacetic acid amide (O.llg, 0.20 minol) was dissolved in 4 ml of tetrahydrofuran by heating, a 1 N aqueous solution of sodium hydroxide (0.2 ml, 0.20 ml) was added, and the mixture was stirred at room temperature for 1 hour.

 After completion of the reaction, the solvent was distilled off under reduced pressure, and the obtained residue was crystallized by adding diethyl ether, followed by filtration, washing with dimethyl ether and drying under reduced pressure to obtain 0.07 g of the title compound as a beige solid. I got it.

m.p .; 178-183 ° C

FAB-MS (m / z); 575 (\ Γ + 1) By the same method as in Example 47, the following compounds of Examples 48 to 49 were obtained. Example 48

[2-[(E) -1 2- (6,7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1 Hydrobenz [b, e] oxepin-111-yl] Thio N-trifluoromethanesulfonyl acetic acid amide sodium salt: (Na salt of Exemplified Compound 23)

Properties: orange solid.

m.p .; 182-186 ° C

FAB-MS (m / z); 629 (M '+ 1)

'.Eta. thigh _{(5, DMS0 - d 6)} ; 2.96 (d, J = 14.4Hz, 1H), 3.06 (d, J = 14.7Hz, 1H), 5.01 (d, J = 12.7Hz, 1H), 5.53 (s, lH), 6.ll (d, J = 12.9Hz, 1H), 6.87 (d, J = 8.3Hz, 1H), 7.34 (d, J = 16.4Hz, 1H), 7.33-7.45 (m, 4H), 7.57 (dd, J = 8.5, 2.0Hz, 1H), 7.71 (d, J = 2.0Hz, 1H), 7.77 (dJ = 16.4Hz, 1H), 7.84 (d, J = 8.6Hz, 1H) , 7.96 (dd, J = 12.0, 8.05Hz, 1H), 8.01 (ddJ = ll.2, 8.8Hz, 1H), 8.35 (d, J = 8.6Hz, 1H)

 (a) 3— [2 — [(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] -6,11-dihydrodibenz [b, e] oxepin-1 11-yl] Thio-N-methanesulfonyl propionamide: (Exemplified compound 27)

Properties: orange solid.

FAB-MS (ra / z); 567 (M '+ 1)

 'H-NMR ^' DMSO-d; 2.65-2.72 (m, 4H), 3.25 (s, 3H), 5.02 (d, J = 12.9Hz, 1H), 5.35 (s, lH), 6.15 (d, J = 12.7Hz, 1H), 6.87 (d, J = 8.3Hz, 1H), 7.35 (1H, J = 16.4Hz, 1H), 7.39-7.46 (ra, 4H), 7.57 (dd, J = 8.6, 2.2Hz) , LH), 7.71 (d, J = 2.2 Hz, 1H), 7.78 (d, J = 16.4 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.94 (dd, J = 12.0, 7.8 Hz) , 1H), 8.03 (dd, J = ll.0, 8.8Hz, 1H), 8.36 (d, J = 8.5Hz, 1H), 11.83 (s, lH)

(b) 3— [2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] -6,11-dihydrodibenz [b, e] oxepin-1 11-yl] Thio-N-methanesulfonyl propionate amide sodium salt

Properties; brown solid

m.p .; 187-192 ° C

FAB-MS (m / z); 589 (M '+ 1) Example 50

 (a) N— t—butoxycarbonyl _N— | 2-[2— [(E) —2— (6,7-difluo-2--1-quinolinyl) ethenyl] 1-6,1 1-dihydrodibenz [b , E] oxepin _ 11 1-yl] thioethyl I trifluoromethanesulfonic acid amide

2-((E) -2-(6,7-Difluoro-2-quinolinyl) ethenyl) 1 1 1- (2-Hydroxitytyl) 1-6,11 dihydrodibenz [b, e] oxepin (0.29g, Was dissolved in 10 ml of tetrahydrofuran, and N-t-butoxycarboyltrifluoromethanesulfonamide (0.26 g, 1.04 ol) and triphenylphosphine (0.26 g, 0.99 ol) were dissolved. In addition, Further, a 2.2 M toluene solution (0.40 ml, 0.88 mmol) of getyl azodicarboxylate was added, and the mixture was added at room temperature.

Stir for 5 hours.

 After completion of the reaction, the reaction solution was concentrated as it was and subjected to silica gel chromatography (eluent: hexane / ethyl acetate = 91 (volume ratio)) to obtain 0.39 g of the title compound as an orange solid. FAB-MS (ra / z); 693 (Μ * + 1)

'H-NMR (0 \ DMS0-d ₆ ); 1.46 (s, 9H), 2.71-2.75 (m, 2H), 3.94-4.07 (m, 2H), 5.04 (d, J = 12.9Hz, IH), 5.39 (s, lH), 6.18 (d, J = 12.9Hz, IH), 6.90 (d, J = 8.3Hz, IH), 7.36 (d, J = 15.9Hz, IH), 7.39-7.49 (m, 4H ), 7.59 (dd ₍ J = 8.6, 2.2Hz, lH), 7.78 (d, J = 2.2Hz, IH), 7.85 (d, J = 16. LHz, IH), 7.95 (dd, J = 11.5, 7.8 Hz, lH), 7.96 (d, J = 8.5Hz, IH), 8.09 (dd, J = ll.0, 8.8Hz, IH), 8.46 (d, J = 8.8Hz, IH)

(b) N-12-[2--((E)-2-(6,7-difluoro-1-2-quinolinyl) ethenyl) -1,6,1 1-dihydrodibenz [b, e] oxepin-1 1 1- Thiyl] trifluoromethanesulfonic acid amide: (Exemplified compound 26)

 N-t-butoxycarbonyl-N- 12-[2-[(E) -2-(6,7-difluoro-2-quinolinyl) ethenyl] 1, 6,11-dihydroxybenz [b, e] oxepin _ 11-yl] Thiechyl I Trifluoromethanesulfonic acid amide (0.14 g, 0.20 mmol) was dissolved in 5 ml of tetrahydrofuran, and 7 ml of trifluoroacetic acid was added, followed by stirring at room temperature for 2 hours until a homogeneous solution was obtained. After completion of the reaction, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. The solvent was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: hexane / ethyl acetate = 9/1 (volume ratio)) to obtain 0.06 g of the title compound as a pale yellow solid. .

m.p .; 84-87 ° C

FAB-MS (m / z); 593 (M '+ 1)

'H-NMR (i, DMS0 -d 6); 2.63 (t, J = 7.1Hz, 2H), 3.29-3.36 (m, 2H), 5.02 (d, J = 12.7Hz, IH), 5.40 (s, IH), 6.20 (dJ = 12.9Hz, IH), 6.88 (d, J = 8.6Hz, IH), 7.35 (d, J = 16.4Hz, IH), 7.38-7.47 (m, 4H), 7.58 (dd, J = 8.3, 2.2Hz, IH), 7.75 (dJ = 2.2Hz, IH), 7.78 (d, J = 16.4Hz, IH), 7.86 (d, J = 8.8Hz, lH), 7.93 (dd, J = ll. 7, 7.8 Hz, IH), 8.03 (ddJ = lL 0, 9.0 Hz, IH), 8.36 (d, J = 8.8 Hz, IH), 9.57 (br.s, lH) Example 51

 (a) 4- [2-trifluoromethanesulfonyloxy-6,11-dihydrodibenz [b, e] oxepin-111] ethyl butyrate

 4- [2-hydroxy-6,11-dihydroxybenz [b, e] oxepin — 11-yl] Ethyl butyrate (0.34 g, l.Ommol) is dissolved in 4 ml of methylene chloride, and triethylamine ( (0.6 ml, 4.3 mmol) and then trifluoromethanesulfonic anhydride (0.4 ml, 2.6 bandol) were added, and the mixture was stirred at room temperature for 20 minutes.

After completion of the reaction, the reaction solution is concentrated, and the obtained residue is subjected to silica gel chromatography (eluent: Hexane ethyl acetate = 92/8 (volume ratio)) to give 0.37 g of the title compound as a pale yellow liquid.

 CI-MS (m / z); 459 (Μ * + 1), EI-MS (m / z); 458 (Μ ')

'H-NMR ((J, CDC1 3); 1.22 (t, J = 7.1Hz, 3H), 1.55 (quintet, J = 7.7Hz 2H) 2.06-2.17 (m, 2H), 2.28 (t, J = 7.3 Hz, 2H), 3.79 (t, J = 7.8Hz, 1H), 4.10 (q, J = 7.1Hz, 2H), 4.98 (d, J = 14.4Hz 1H) 5.52 (d, J = 14.4Hz, 1H) , 6.99-7.12 (m 4H) 7.18-7.25 (m, 3H)

(b) 4- [2-[(E) -1- (6-, 7-difluoro-2-quinolinyl) ethenyl] -1,6,11-dihydrodibenz [be] oxepin-111] butanoic acid Etil

 4- [2-Trifluoromethanesulfonyloxy-611-dihydrodibenz [be] oxepin-111-yl] Ethyl butanoate (0.36 g 0.79 mmol) is dissolved in 5 ml of NN-dimethylformamide. Tetra-n-butylammonium chloride (0.27 g 0.97 ol), sodium hydrogen carbonate (0.33 g 3. llmmol), lithium bromide (0.12 g 1.38 ol), 67-difluoro-2-vinylquinoline (0.30 g 1.57 mmol) and tetrakis (triphenylphosphine) palladium (0) (70 rag, 0.06 mmol) were added in this order, and the mixture was stirred at room temperature for 6 hours under an argon atmosphere.

 After completion of the reaction, water was added to the reaction solution, extracted with toluene, and the organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: hexane ethyl acetate = 9Z1 (volume ratio)) to obtain 91rag of the title compound as a yellow solid.

CI-MS (m / z); 500 (M '+ 1), EI-MS (m / z); 499 ()

Ή-thigh (ό CDC1 ₃ ); 1.23 (t, J = 7.1Ηζ, 3Η), 1.61 (quintet, J = 7.3Hz, 2H), 2.05-2.27 (m, 2H), 2.30 (t J = 7.1Hz 2H ), 3.85 (t J = 7.8Hz 1H) 4.10 (q, J = 7.1Hz, 2H), 5.00 (d J = 14.4Hz, 1H), 5.56 (d J = 14.2Hz lH), 6.99 (d, J = 8.8Hz, 1H), 7.11-7.14 (m, 1H), 7.19-7.24 (m, 4H), 7.43- 7.45 (m2H), 7.50 (dd, J = 10, 3 8.3Hz 1H) 7.61 (d J = 8.6Hz 1H) 7.64 (d, J = 15.9Hz, 1H) 7.80 (dd, J = 11.2 ₍ 7.8Hz, 1H), 8.04 (d, J = 8.8Hz 1H)

(c) 41- [2-[(E) -2- (67-difluoro-2-quinolinyl) ethenyl] 1 6 1 1-dihydrodibenz [b, e] oxepin_11-yl] Butanoic acid Sodium salt: (Exemplary compound 32 sodium salt)

 4 -— [2 -— ((E) —2 -— (6,7-difluoro-2-quinolinyl) ethenyl) 1 6 1 1 1 dihydrodibens [be] xepin-1 1-yl] Ethyl butanoate (133 mg) (0.27 mmol) was dissolved in 2 ml of dioxane, 2 ml of a 2 N aqueous solution of sodium hydroxide was added, and the mixture was stirred at room temperature for 2 hours.

After completion of the reaction, 4 ml of 1N hydrochloric acid was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated. Next, the obtained concentrated residue was dissolved in tetrahydrofuran (2 ml), and concentrated by adding a 1 N aqueous solution of sodium hydroxide (0.25 ml 0.25 ol). Gechel ether was added to the obtained residue, and the resulting precipitate was collected by filtration. (S 2 ΐ ΐ ^^ U): nj

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90l760 / 00df / X3d 688m OAV 2 — [(E) —2— (5,6,7,8-tetrahydro-1-2-quinolinyl) ethenyl] 1 1 1—Methoxy 8—Methoxycarbonyl 6,11 Dihydrodibenz [b, e ] Oxepin (0.20 g, 0.45 ol) was dissolved in methylene chloride (40 ml), and 3-mercaptopropionic acid (0.14 ml, 0.54 mol) was added. ) Was added for tl, and the mixture was stirred at room temperature for 4 hours.

 After the completion of the reaction, water was added to the reaction solution, the pH was adjusted to about 6.0 with a saturated aqueous solution of sodium hydrogen carbonate, and the mixture was extracted with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated. The obtained residue was crystallized by adding getyl ether, and then filtered. The obtained crystals were washed with getyl ether and dried under reduced pressure to obtain 0.17 g of the title compound as a yellow solid.

m.p.; 121-123 ° C

FAB-MS (m / z); 516 (M ++ 1)

 'Η-thigh (S'DMSO-de); 1.60-1.90 (m, 4H), 2.60-2.90 (m, 4H), 3.87 (s, 3H), 5.15 (d, J = 12.9Hz, IH), 5.43 (s, lH), 6.09 (dJ = 12.7Hz, lH), 6.84 (d, J = 8.3Hz, IH), 7.10 (d, J = 15.9Hz, IH), 7.28 (d, J = 8.1Hz, IH ), 7.43 (d, J = 8.3 Hz, IH), 7.47 (d, J = 16.1 Hz, IH), 7 · 48 (dd, J = 8.5, 2.2 Hz, IH),

 7.54 (d, J = 7.8Hz, 1H), 7.62 (dJ = 2.2Hz, IH), 7.95 (dd, J = 7.8, 2.0Hz, IH), 8.04 (d, J = 1.7Hz, IH) In the same manner as in 2, the following compounds of Examples 54 to 58 were obtained. Example 54

 (a) 3-| [9-[(E)-2-(6,7-difluoro-2-quinolinyl) ethenyl]-6,11-dihydrodibenz [b, e] oxepin- 1 1-yl] Thio I propionic acid: (Example compound 404)

Properties: yellow-green solid

Thigh (<5, DMS0_d ₆ ); 2.63-2.73 (m, 4H), 5.00 (d, J = 13.2 Hz, IH), 5.33 (s, IH), 6.10 (d, J = 12.9 Hz, IH), 6.83 (d, J = 8.2Hz, IH), 6.96 (t, J = 7.OHz, IH), 7.19 (t, J = 7.6Hz, IH), 7.33 (d J = 7.9Hz, IH), 7.48 (d , J = 10.7Hz, lH), 7.52 (d, J = 19.2Hz, IH), 769 (d, J = 7.8Hz, IH), 7.82-8.08 (m, 5H), 8.38 (d, J = 8.8Hz, IH)

(b) 3— | [9-[(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] 1-6,11-dihydrodibenz [b, e] oxepin ] Chio sodium propionate

Properties: yellowish white solid

m.p.;> 300 ° C

FAB-MS (m / z); 512 (M '+ 1) Example 55

 (a) 3— | [3-[(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1 10, 1 1 dihidro 5H—dibenz [a, d] cycloheptene 1-5-yl Thio 1 2— (S) monomethylpropionic acid: (Exemplified compound 385)

Properties: yellow-green solid

'H-NMR (S, DMS0 -d 6); 1.05 (d, J = 6.8Hz, 3H), 2.41-2.73 (m, 3H), 2.87 (m, 2H), 3.70-3.74 (m, 2H), 5.33 (s, lH), 7.15-7.25 (m, 4H), 7.33 (d, J = 6. Hz, IH), 7.46 (d, J = 16.4 Hz, IH), 7.57 (d, J = 7.8 Hz, IH), 7.72 (s, 1H), 7.81 (d, J = 16.6Hz, IH), 7.91 (dd, J = 8.6, 2.7Hz, IH), 7.96 (dd, J = 9.2, 3.7Hz, IH), 8.04 (dd, J = ll.l, 8.9Hz, lH), 8.34 (dJ = 8.8Hz, IH)

(b) 3— | [3— [(E) -1-2- (6,7-difluoro-2-quinolinyl) ethenyl] —10,11-dihydro-5H-dibenz [a, d] cycloheptene-5— Thiol I —2— (S) Sodium monomethylpropionate

Properties: white powder

m.p.; 211-22 (TC

 FAB-MS (m / z); 524 (M '+ 1) Example 56

 (a) 3— | [2— [(E) — 2— (6-Fluoro-7-trifluoromethyl-1-2-quinolinyl) ethenyl] -1,6,1 1-dihydrodibenz [b, e] oxepin 1 1—Ill! Propionic acid: (Exemplary compound 352)

Properties: pale yellow solid

FAB-MS (m / z); 540 (M '+ 1)

 'Η-thigh (<5, DMS0-); 2.45-2.80 (m, 4H), 5.02 (d, J = 12.9Hz, IH), 5.37 (s, IH), 6.19 (d, J = 12.7Hz, 1H ), 6.88 (d, J = 8.5 Hz, lH), 7.30-7.50 (m, 5H), 7.58 (dd, J = 8.5, 2.2 Hz, IH), 7.72 (dJ = 2.2 Hz, IH), 7.84 (d , J = 16.4Hz, IH), 8.06 (d, J = 8.5Hz, IH), 8.08 (d, J = ll.2Hz, IH), 8.35 (d, J = 6.8Hz, IH), 8.44 (d, J = 8.8Hz, IH), 12.0-12.7 (br, s, IH)

(b) 3— | [2-((E) —2— (6 _fluoro-7-trifluoromethyl-2-quinolinyl) ethenyl] 1, 6 1 1-dihydrodibenz [b, e] oxepin 1 1 1-yl] thio i sodium propionate

Properties: yellow solid

m.p .; 221-224 ° C (decomposition)

FAB-MS (m / z); 494 (+1) Example 57 (a) 3—j [2-[(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] -1-8-fluoro-6,11-dihydroxybenz [b, e] oxepin-1 1 Iyl] Thio I propionic acid: (Exemplified compound 44)

Properties: yellow solid

Ή- thigh _{(<J, DMS0-d 6} );. 8.35 (d, J = 8.6Hz, 1H), 8.06-7.31 (ra, 9H), 7.22 (td, J = 9 OHz, J = 2.7Hz, IH ), 6.89 (d, J = 8.6Hz, 1H), 6.13 (d, J = 12.9Hz, IH), 5.42 (s, lH), 5.03 (d, J = 12.9Hz, IH), 2.66 (t, J = 5.9Hz, 2H), 2.53 (t, J = 6.1Hz, 2H)

(b) 3-1C 2-[(E) 1 2— (6,7-difluoro-2-quinolinyl) ethenyl] 1 8-fluoro-6,1 1-dihydroxybenz [b, e] oxepin 1 1 1 Zyl) Sodium I propionate

Properties; light yellow glossy solid

m.p .; 243-250 ° C. Example 58

 3— | [2-[(E) —2— (6,7-Difluoro-2-quinolinyl) ethenyl] 1 6, 1 1—Dihydrodibenz [b, e] oxepin 1 1 1-yl] — 3-Methylbutanoic acid: (Example compound 12 sodium salt)

Properties; pale yellow solid

FAB-MS (m / z); 540 (M ⁺ +1)

 'Η-thigh (<J, DMS0_); 1.36 (s, 3H), 1.39 (s, 3H), 2.29 (d, J = 18.7Hz, IH), 2.34 (d, J = 18.7Hz, IH), 4.99 (d, J = 12.8Hz, lH), 5.64 (s, lH), 6.24 (d, J = 12.8Hz, IH), 6.80 (d, J = 8.5Hz, IH), 7.30-7.80 (m, 8H) , 7.90 (d, J = 8.8Hz, IH), 7.97 (dd, J = 8.1,7.8Hz, IH), 8.02 (dd, J = ll.2, 9.OHz, IH), 8.34 (d, J = (8.8Hz, IH) Reference example 1

 (a) 2 — [(E) 1—2— (7_Chloro-1-6-fluoro-2-quinolinyl) ethenyl] -6,1 1 Dihydrodibenz [b, e] Oxepin 1 1 1

 7-Chloro-1-6-fluoroquinaldine (0.82 g, 4.20 ol) and 2-formyl-6,11 dihydrodibenz [b, e] oxepin-111-one (l.OOg, 4.20 (mmol) with acetic anhydride was stirred at 125 ° C for 72 hours.

After completion of the reaction, the reaction mixture was concentrated under reduced pressure, a saturated aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated. The obtained residue was subjected to silica gel chromatography (eluent: toluene-toluene ethyl acetate = 251 (by volume)) to give 1.40 g of the title compound as a tan solid. E - visceral _{(S'DMSO- d 6); 5.36 (} s, 2H), 7.20 (d, J = 8.5Hz, 1H), 7.49 (d, J = 8.5Hz, IH), 7.50-7.75 (m, 5H ), 7.73 (dd, J = 8.5, 2, 4 Hz, lH), 7.80 (d, J = 7.8 Hz, IH), 7.96 (d, J = 9.8 Hz, IH), 8.14 (d, J = 7.3 Hz, 1H), 8.23 (d, J = 2.0Hz, lH), 8.26 (d, J = 8.5Hz, 1H)

(b) 2-[(E) -2- (7-chloro-1-6-fluoro-2-quinolinyl) ethenyl] 1 1 1-hydroxy 6,1 1-dihydroxybenz [b, e] oxepin

 2-[(E) —2— (7-chloro-1-6-fluoro-2-quinolinyl) ethenyl] _6,11-dihydrodibenz [b, e] oxepin-11-one (1.40 g, 3.47 mmol ) Was suspended in a mixture of 40 ml of tetrahydrofuran and 40 ml of methanol, sodium borohydride (0.16 g, 4.16 mL) was added, and the mixture was stirred at room temperature overnight.

 After completion of the reaction, the reaction mixture was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: toluene to toluene / ethyl acetate = 9: 1 (volume ratio)) to give 0.77 g of the title compound as a yellow solid. Obtained.

 FAB-MS (ra / z); 418 (M '+ 1)

'.Eta. Hokusatsu _{(S.DMSO- d 6); 5.30 (} d, J = 12.2Hz, lH), 5.77 (d, J = 14.2Hz, 1H), 5.97 (d, J = 3.9Hz, 1H), 6.27 (d, J = 3.9Hz, 1H) ₍ 6.83 (d, J = 8.5Hz, 1H), 7.25-7.60 (m, 5H), 7.70 (dd, J = 8.5, 2.2Hz, 1H), 7.80 (d, J = 15.6Hz, 1H), 7.92 (d, J = 8.8Hz, 1H) Reference Example 2

 (a) 2— [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1, 6, 1 1—dihydrodibenz [b, e] oxepin

 [(6,7-Difluoro-2-quinolinyl) methyl] triphenylphosphonium bromide

(1.35g, 2.59mmol) in 15ml suspension of tetrahydrofuran at -78 ° C.

1.7 ml of a 57 M hexane solution was added to the solution D, and the mixture was stirred at the same temperature for 30 minutes. Then, 2-formyl

6,11 Dihydrobenz [b, e] oxepin-111 (0.59 g, 2.48 mmol) in 15 ml of tetrahydrofuran was added over 1-5 minutes over 15 minutes, and then stirred at the same temperature for 1 hour. did. After completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. The resulting residue was subjected to silica gel chromatography (eluent: toluene / ethyl acetate = 97/3 (volume ratio)) to obtain 0.31 g of the title compound as a yellow solid.

CI-MS (m / z); 399 (M *), EI-MS (m / z); 399 (Μ ^÷ )

'Η-thigh, the hall. -): 5.37 (s, 2H), 7.19 (d, J = 8.8 Hz, 1H), 7.44 (d, J = 15.9 Hz, 1H), 7.54-7.62 (ra, 2H), 7,68 (d, J = 7.3Hz, lH), 7.82 (d, J = 7.8Hz, 1H), 7.97—8.07 (m, 5H), 8.36-8.39 (in, 2H)

(b) 2-[(E) 1-2-(6,7-difluoro-2-quinolinyl) ethenyl] 1-1-Hydrox-1, 6-1 -Hydroxybenz [b, e] oxepin

2— [2— (6,7-Difluoro-2_quinolinyl) ethenyl] 1-6,1 1-Dihydrobenz [b, e] oxepin 1 1 1 1 year old (0.31g, 0.77 recital ol) (E) — 2- (7-chloro-6-fluoro-2-quinolinyl) ethenyl] 1, 6,1 1-dihydrodibenz [b, e] The reaction was carried out in the same manner as in Reference Example 1 (b), except that oxepin-1 1-one was used instead of oxepin-1-1-one, to obtain 0.10 g of the title compound as a yellow solid.

CI-MS (m / z); 401 (M, EI-MS (m / z); 401 (Μ ')

'H-NMR (0 \ DMS0-d ₆ ); 5.38 (d, J = 12.4Hz, 1H), 5.76 (d, J = 12.2Hz, IH), 5.94 (s, IH), 6.24 (s, IH) , 6.82 (d, J = 8.5Hz, IH), 7.28-7.50 (m, 5H), 7.56 (dd, J = 8.5, 2.2Hz, IH), 7.76-7.82 (m, 2H), 7.88 (d, J = 8.8Hz, IH), 7.93 (dd, J = 12.0, 8.0Hz, lH), 8.01 (dd, J = ll.2, 9.OHz, IH), 8.33 (d, J = 8.5Hz, IH) Reference In the same manner as in Example 2, the following compounds of Reference Examples 3 to 13 were obtained. Reference example 3

 (a) 2— [(E) — 2— (7-Fluoro-2-quinolinyl) ethenyl] _ 6,1 1-dihydrodibenz [b, e] oxepin-1 1-one

Properties: light yellow solid

CI-MS (ra / z); 382 (M ^÷ + 1), EI-MS (m / z); 381 (M *)

'.Eta. thigh _{(<J, DMS0- d 6)} ; 5.38 (s, 2H), 7.19 (d, J = 8.5Hz, IH), 7.45 (d, J = 16.4Hz, IH), 7.49 (td, J = 8.8,2.7Hz, IH), 7.57 (t, J = 7.6Hz, 1H), 7.61 (d, J = 6.6Hz, IH), 7.65-7.75 (m, 2H), 7.82 (d, J = 7.6Hz , lH), 7.91 (d, J = 8.5 Hz, lH), 7.94 (dJ = 16. Hz, IH), 8.00-8.15 (m, 2H), 8.37 (d, J = 2.2 Hz, 1H), 8.40 ( d, J = 8.5Hz, IH) (b) 2— ((E) —2— (7-Fluoro-2-quinolinyl) ethenyl) 1 1 1—Hydroxy 6,11 Dihydrodibenz [b, e] oxepin

Properties: tan solid

 CI-MS (m / z); 384 (Μ * + 1), EI-MS (ra / z); 383 (M *)

 ¾-thigh (S, DMS0-); 5.29 (dJ = 12.5 Hz, IH), 5.78 (d, J = 12.2 Hz, IH), 5.96 (d, J = 3.7 Hz, IH), 6.26 (d, J = 3.9Hz, 1H), 6.83 (d, J = 8.3Hz, IH), 7.25-7.55 (m, 5H), 7.33 (dJ = 16.Hz, IH), 7.57 (dd, J = 8.5, 2.2Hz, lH ), 7.69 (dd, J = 10.7, 2.7Hz, IH), 7.81 (d, J = 10.7Hz, IH), 7.82 (d, J = 2.0Hz, IH), 7.84 (d, J = 8.8Hz, IH ), 8.02 (dd, J = 8.8, 6.6Hz, IH), 8.37 (d, J = 8.5Hz, IH) Reference example 4

 (a) 2-[(E) — 2— (7—chloro-1-2-quinolinyl) ethenyl] 1, 6 1 1—dihydrodibenz [b, e] oxepin 1 1—one

Properties: light yellow solid

 CI-MS (m / z); 398 (M '+ 1), EI-MS (m / z); 397 (M *)

'Η-hidden (<J, DMS0-d ₆ ); 5.38 (s, 2H), 7.19 (d, J = 8.5Hz, IH), 7.45 (d, J = 16.4Hz, IH), 7.50-7.75 (m , 4H), 7.82 (d, J = 7.6 Hz, IH), 7.94 (d, J = 16. lHz, IH), 7.96 (d, J = 8.5 Hz, IH), 8.00 (dJ = 8.8 Hz, 1H) , 8.02 (d, J = 1.7Hz, 1H), 8.06 (dd, J = 8.5, 2.4Hz, 1H), 8.36 (d, J = 2.2Hz, IH), 8.40 (dJ = 8.8Hz, IH) (b) 2— [(E) — 2— (7-chloro-2-quinolinyl) ethenyl] 1 1 1-hydroxy-6,1 1-dihydrobenzen [b, e] oxepin

Properties: yellow solid

CI-MS (m / z); 399 (M '), EI-MS (m / z); 399 (Μ ^÷ )

'Η-thigh (ό ヽ, DMSO-d ₆ ); 5.28 (d, J = 12.4 Hz, lH), 5.76 (d, J = 12.2 Hz, IH), 5.95 (d, J = 3.7 Hz, IH), 6.24 (d, J = 3.9Hz, 1H), 6.82 (d, J = 8.5Hz, IH), 7.25-7.55 (m, 5H), 7.57 (dd, J = 8,8,2.2Hz, 2H), 7.81 (d, J = 16.4Hz, 1H), 7.81 (d, J = 2.OHz, IH), 7.89 (d, J = 8.8Hz, IH), 7.98 (d, J = 8.8Hz, IH), 8.00 ( d, J = 1.7Hz, 1H), 8.36 (d, J = 8.8Hz, IH) Reference example 5

 (a) 2-((E) —2— (5,6,7,8-tetrahydro-2-quinolinyl) ethenyl) 1, 6,1 1 dihydrodibenz [b, e] oxepin 1 1—one

Properties: yellow solid

CI-MS (m / z) ; 368 (M '+ 1), EI-MS (m / z); 367 (),' H-NMR (0 \ DMS0-d c); 5.34 (s, 2H), 7.14 (d, J = 8.5Hz, IH), 7.20 (d, J = 16.1Hz, IH), 7.34 (d,

J = 8.1Hz, IH), 7.43 (d, J = 8.1Hz, IH), 7.50-7.75 (m, 3H), 7.59 (d, J = 16.1Hz, IH), 7.81 (d, J = 7.1Hz, 1H), 7.93 (dd, J = 8.5, 2.2Hz, IH), 7.26 (dJ = 2.2Hz, IH)

(b) 2-[(E) —2— (5,6,7,8-tetrahydro-2-quinolinyl) ethenyl] 1 1 1-hydroxy-1 6,11 dihydrodibenz [b, e] oxepin

Properties: light yellow solid

 CI-MS (m / z); 370 (M * + 1), EI-MS (m / z); 369 (Μ ')

'Eta - thigh _{(S.DMSO- d 6); 2.70-2.90 (} m, 4H), 2.73 (t, J = 6.3Hz, 2H), 2.82 (t, J = 6.3Hz, 2H), 5.23 (d, J = 12.5Hz, IH), 5.75 (d, J = 12.2Hz, IH), 5.89 (s, lH), 6.17 (d, J = 3.4Hz, IH), 6.77 (d, J = 8.5Hz, IH) , 7.07 (d, J = 16.1Hz, lH), 7.20-7.55 (m, 8H), 7.69 (d, J = 2.2Hz, IH) Reference example 6

 (a) 2-[[(E) -2- (4-chloro-1--2-quinolinyl) ethenyl] 1,6,11-dihydrodibenz [b, e] oxepin _ 1 1one

Properties: yellow solid

 CI-MS (m / z); 398 (M '+ 1), EI-MS (m / z); 397 (M *)

'H-Awake (ό, DMSO-); 5.38 (s, 2H), 7.19 (d, J = 8.8 Hz, IH), 7.42 (d, J = 16.4 Hz, IH), 7.57 (td, J = 7.6 , 1.2Hz, lH), 7.61 (d, J = 6.6Hz, IH), 7.65-7.75 (m, 2H), 7.83 (dd, J = 7.3, 1.5Hz, IH), 7.86 (ddd, J = 8.5, 7.1, 1.5Hz, lH), 7.99 (d, J = 16.6Hz, IH), 8.05 (dd, J = 8.5, 2.4Hz, IH), 8.07 (d, J = 7.8Hz, 1H) _: 8.16 (dd, J = 8.5, 1.5Hz, IH), 8.20 (s, lH), 8.38 (d, J = 2.2Hz, IH)

(b) 2-[(E) — 2- (4-chloro-2-quinolinyl) dienyl] 1 1 1-hydroxy 6, 1 1—dihydrodibens [b, e] oxepin

Properties: yellow solid

 CI-MS (m / z); 400 (M '+ 1), EI-MS (m / z); 399 (Μ')

'.Eta.賺_{(<J, DMS0_d c);} 5.29 (d, J = 12.5Hz, IH), 5.76 (d, J = 12.5Hz, IH), 5.95 (d, J = 3.4Hz, 1H), 6.24 ( d, J = 3.9Hz, lH), 6.82 (d, J = 8.3Hz, IH), 7.30 (d, J = 16.4Hz, IH), 7.30-7.45 (m, 3H), 7.48 (dd, J = 6.8 , 2. OHz, IH) '7.57 (dd, J = 8.5, 2.2 Hz, IH), 7.69 (ddd, J = 8.3, 6.8, 1.2 Hz, IH), 7.82 (d, J = 2.2 Hz, lH), 7.85 (dddJ = 8.3, 6.8, 1.2 Hz, 1H), 7.86 (d, J = 16.4 Hz, IH), 8.04 (d, J = 8. lHz, IH), 8.12 (s, IH), 8.15 ( d, J = 8.3Hz, lH) Reference Example 7

 (a) 2— [(E) — 2— (5-fluoro-2-quinolinyl) ethenyl] 1, 6, 1 1 -dihydrodibenz [b, e] oxepin 1 1 1-one

Properties: yellow solid

 CI-MS (m / z); 382 (M '+ 1), EI-MS (m / z); 381 ()

 -Thigh (S, DMS0-; 5.38 (s, 2H), 719 (d, J = 8.5 Hz, 1H), 7.38 (dddJ = 10.0, 7.8, 1. OHz, IH),

7.47 (d, J = 16.4Hz, lH), 7.57 (td, J = 7.3,1.2Hz, IH), 7.61 (d, J = 7.3Hz, IH), 7.70 (td, J = 7.3,1.5Hz, 1H ), 7.75 (td, J = 7.8, 6.1 Hz, lH), 7.83 (dd, J = 7.8, 1.2 Hz, IH), 7.85 (d, J = 8.5 Hz, IH), 7.96 (d, J = 15.6 Hz) , IH), 8.00 (d, J = 8.5Hz, lH), 8.05 (dd, J = 8.8, 2.4Hz, IH), 8.38 (d, J = 2.2Hz, IH), 8.46 (d, J = 9.0Hz , IH)

(b) 2— [(E) — 2— (5-Fluoro-2-quinolinyl) ethenyl] 1 1 1-Hydroxy-1,6,1 1-Hydroxybenz [b, e] oxepin

Properties: yellow solid

CI-MS (m / z); 384 (M '+ 1), EI-MS (m / z); 383 (Μ ^÷ )

'Η-thigh, DMSO- d _r '); 5.28 (d, J = 12.2Hz, IH), 5.78 (d, J = 12.5Hz, IH), 5.94 (s, lH), 6.83 (d, J = 8.3 Hz, lH), 7.25-7.55 (m, 5H), 7.58 (dd, J = 8.3, 2.2Hz, IH), 7.30-7.60 (m, IH), 7.75-7.90 (m, 3H), 7.94 (d, J = 8.8Hz, IH), 8.44 (d, J = 8.8Hz, IH) Reference Example 8

 (a) 2 — [(E) —2— (5,7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1 dihydrodibenz [b, e] oxepin 1 1 1 _one

Properties: light yellow solid

CI-MS (m / z); 400 (M ⁴ +1), EI-MS (m / z); 399 (Μ ')

'Η-thigh, DMSO- d ₆ ); 5.38 (s, 2H), 7.20 (d, J = 8.5Hz, IH), 7.46 (d, J = 16.4Hz, 1H), 7.45-7.65 (m, 4H) , 7.70 (td, J = 7.6, 1.5Hz, 1H), 7.82 (dd, J = 7.8, 1.2Hz, IH), 7.97 (d, J = 9.OHz, IH), 7.98 (d, J = 15.4Hz , lH), 8.05 (dd, J = 8.8.2.4Hz, IH), 8.37 (d, J = 2.2Hz, 1H), 8.46 (d, J = 8.5Hz, IH) (b) 2-[(E) 1-2-(5,7-Fluoro-2-quinolinyl) ethenyl] 1-1-Hydroxie 6, 11-Dihydrodivenes [b, e] oxepin

Properties: yellow solid

 CI-MS (m / z); 402 (M '+ 1), EI-MS (m / z); 401 (Μ')

'Η-thigh (S'DMSO-: 5.29 (d, J = 12.5Hz, IH), 5.77 (d, J = 12.5Hz, IH), 5.94 (s, 1H), 6.26 (d, J = 3.9Hz, 1H), 6.83 (d, J = 8.3Hz, lH), 7.25-7.65 (ra, 6H), 7.82 (d, J = 2.2Hz, IH), 7.87 (d, J = 17.3Hz, 1H), 7.91 ( d'J = 9.0Hz, lH), 8.3 (d, J = 9. OHz, IH) Reference example 9

 (a) 2— [(E) — 2— (6-Fluoro-7-trifluoromethyl-12-quinolinyl) ether] 1,6,1 1-Dihydrodibenz [b, e] oxepin — 1 1 one on

Properties: yellow solid

 CI-MS (m / z); 450 (M '+ 1), EI-MS (m / z); 449 (Μ')

 'Η-thigh (<J, DMS0-); 5.38 (s, 2H), 7.20 (dJ = 8.5Hz, IH), 7.47 (d, J = 16.4Hz, 1H), 7.57 (t, J = 7.6Hz, IH), 7.61 (d, J = 7.8Hz, lH), 7.70 (t, J = 7.3Hz, IH), 7.82 (d, J = 7.6Hz, IH), 7.99 (d, J = 16.4Hz, lH) , 8.07 (d'J = 8.1Hz, lH), 8.10 (d, J = 10.3Hz, IH), 8.13 (d, J = 8.1Hz, IH), 8.30- 8.45 (ra, IH), 8.37 (d, J = 2.4Hz, IH), 8.47 (d, J = 8.8Hz, IH)

(b) 2-[(E) — 2— (6-fluoro-7-trifluoromethyl-12-quinolinyl) ethynyl] 1-11-hydroxy-1-6,11-dihydrodibenz [b , E] oxepin

Properties: yellow solid

 CI-MS (m / z); 452 (M '+ 1), EI-MS (m / z); 451 (M *)

'H-NMR (δ, DMS0-d ₆ ); 5.30 (d, J = 12.5 Hz, IH), 5.76 (d, J = 12.5 Hz, IH), 596 (br.s, IH), 6.25 ( br.s, 1H), 6.83 (d, J = 8.5Hz, IH), 7.30-7.55 (m, 4H), 7.34 (d, J = 16.1Hz, 1H), 7.57 (dd, J = 8.5, 2.2Hz , 1H), 7.82 (d, J = 2.4Hz, IH), 7.86 (d, J = 16.6Hz, IH), 8.05 (d, J = 8.8Hz, IH), 8.07 (d, J = ll.2Hz, IH), 8.34 (d, J = 6.8 Hz, 1H), 8.42 (d, J = 8.8 Hz, IH) Reference example 10

 (a) 2 — [(E) 1 2— (5,6,7-trifluoro-2-quinolinyl) ethenyl] 1-6,11-dihydrodibenz [b, e] oxepin 1 1-one

Properties: yellow solid

 CI-MS (m / z); 418 (M '+ 1), EI-MS (m / z); 417 (*)

'Η- 赚, DMSO-): 5.37 (s, 2H), 7.18 (d, J = 8.5 Hz, IH), 7.44 (d, J = 16.4 Hz, IH), 7.57 (td, J = 7.6, 1.5 Hz , IH), 7.60 (d, J = 7.8 Hz, lH), 7.69 (td, J = 7.6, 1.5 Hz, IH), 7.81 (dd, J = 7.6, 1.0 Hz, IH), 7.80-7.95 (m, lH), 7.96 (d, J = 16.1Hz, 1H), 8.03 (d, J = 8.8Hz, IH), 8.04 (dd, J = 8.5, 2.4Hz, IH), 8.36 (d, J = 2.2Hz, IH), 8, 50 (d, J = 8.8Hz, IH)

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(b) 6,7-Difluoro-2-[((E) -2- (4-hydroxyphenyl) ethenyl] quinoline

 2-[(E) —2— (4-Acetoxyphenyl) ethenyl] _6,7-Difluoroquinoline (5.21 g, 16.0 mmol) is suspended in a mixture of 30 ml of dimethyl sulfoxide and 20 ml of methanol, and A solution of sodium oxide (1.13 g, 28.3 mmol) dissolved in 10 ml of water was added, and the mixture was stirred at room temperature for 20 minutes.

 After completion of the reaction, 30 ml of 1N hydrochloric acid was added to the reaction solution to make it acidic, and the precipitated crystals were extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated to obtain 4.20 g of the title compound as a yellow solid.

CI-MS (m / z); 284 (M '+ 1), EI-MS (m / z); 282 (Μ'-1)

'Η-thigh (ό ヽ, DMSO- d ₆ ); 6.81-6.84 (m, 2H), 7.23 (d, J = 16.1 Hz, IH), 7.55-7.58 (ra, 2H), 7.75 (d, J = 16.1Hz, IH), 7.84 (d, J = 8.8Hz, IH), 7.92 (dd, J = 12.0, 8.0Hz, IH), 8.00 (dd, J = ll.0, 8.8Hz, IH), 8.32 ( d, J = 8.8Hz, IH), 9.81 (br.s, IH)

(c) 2- [4-[(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] phenoxymethyl] -13-methyl cyanobenzoate

 6,7-Difluoro-2 _ [(E) — 2- (4-hydroxyphenyl) ethenyl] quinoline (0.40 g, 1.41 mmol) in dimethyl sulfoxide 5ral solution was charged with methyl 2-bromomethyl-13-cyanobenzoate (0.29 g, 1.14 mraol) in 5 ml of dimethyl sulfoxide was added, and potassium carbonate (0.38 g, 2.75 bandol) was further added, followed by stirring at 70 ° C. for 1 hour under a nitrogen atmosphere.

 After completion of the reaction, water was added to the reaction solution, extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: toluene / ethyl acetate = 99/1 (volume ratio)) to obtain 0.52 g of the title compound as a yellow solid.

CI-MS (m / z); 457 (M * + 1), EI-MS (m / z); 456 (Μ ')

3.85(s，3H)， 5.59(s,2H), 7.01-7.04 (m,2H), 7.22(d, J=16.4Hz, IH), 7.49(dd,J=10.0，8.3Hz, IH), 7.54-7.63 (m, 4H), 7.66(d, J=16.1Hz, IH) , 7.80(dd, J=ll.5, 7.8Hz, IH), 7.87(dd,J=7.8, 1.5Hz, IH), 8.03(d， J=8.6Hz, IH)， 8.10(dd, J=8.1, 1.5Hz, IH)

3.85 (s, 3H), 5.59 (s, 2H), 7.01-7.04 (m, 2H), 7.22 (d, J = 16.4Hz, IH), 7.49 (dd, J = 10.0, 8.3Hz, IH), 7.54 -7.63 (m, 4H), 7.66 (d, J = 16.1Hz, IH), 7.80 (dd, J = ll.5, 7.8Hz, IH), 7.87 (dd, J = 7.8, 1.5Hz, IH), 8.03 (d, J = 8.6Hz, IH), 8.10 (dd, J = 8.1, 1.5Hz, IH)

(d) 3-cyano 2- [4-[((E) -2- (6,7-difluoro-2-quinolinyl) ethenyl] phenoxymethyl] benzoic acid

3-cyano-2- [4-1 ((E) -2- (6,7-difluoro-2-quinolinyl) ethenyl] phenoxymethyl] Methyl benzoate (0.52 g, 1.14 t) was suspended in 30 ml of dioxane, and A solution prepared by dissolving sodium oxide (0.48 g, 12.0 tmol) in 1 ml of water was added, and the mixture was stirred at room temperature for 30 minutes until a homogeneous solution was obtained.

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J = 8.5Hz, 2H), 7.85 (d, J = 16.4Hz, 1H), 7.93 (d, J = 8.5Hz, 1H), 7.99 (d, J = 9.5Hz, 1H), 8.20 (d, J = 7.3 Hz, lH), 8.37 (d, J = 8.5 Hz, lH) The following compound of Reference Example 16 was obtained in the same manner as in Reference Example 14 (b). Reference Example 1 6

 7-Black 1-Fluoro-2-[(E) -1-2- (4-Hydroxyphenyl) ethenyl]

Properties: yellow solid

 CI-MS (m / z); 300 (M '+ 1), EI-MS (m / z); 298 (Μ'-1)

'Eta - Anonymous _{(<J, DMS0- d 6)} ; 6.83 (d, J = 8.5Hz, 2H), 7.23 (d, J = 16.4Hz, 1H), 7.57 (d, J = 8.8Hz, 2H), 7.76 (d, J = 16.4Hz, lH), 7.89 (d, J = 8.8Hz, 1H), 7.97 (d, J = 10.OHz, 1H), 8.17 (d, J = 7.3Hz, 1H), 8.32 (d, J = 8.8Hz, 1H), 9.84 (br. s, 1H) Reference Example 1 7

 2-Methyl _ 3-Methyl trimethylsilylethynylbenzoate

 Methyl 3-iodo-2-methylbenzoate (1.20 g, 4.35 mmol) and copper (I) iodide (0.21 g,

1.10 bandol) was suspended in 10 ml of tetrahydrofuran, and triethylamine (3.0 ml, 21.5 mmol) and trimethylacetylene (1.5 ral, 10.8 mmol) were added to make a homogeneous solution. Subsequently, tetrakistriphenylphosphine palladium (0) (0.72 g, 0.62 ol) was added, and the mixture was stirred at room temperature under an argon atmosphere for 5 hours.

 After completion of the reaction, water was added to the reaction solution, extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous solution of ammonium chloride and then with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. The solvent was concentrated and the obtained residue was subjected to silica gel chromatography (eluent: hexane Z ethyl acetate = 99/1 (volume ratio)) to obtain 1.05 g of the title compound as a black-brown oil ^! Was.

CI-MS (m / z); 247 (M '+ 1), EI-MS (m / z); 246 (Μ')

0.27(s,9H), 2.70(s，3H), 3.89(s，3H), 7.17(t, J=7.8Hz, 1H), 7.58(dd， J=7.8， 1.5Hz, 1H) , 7.78 (dd， J=7.8, 1.5Hz, 1H) 参考例 1 8

0.27 (s, 9H), 2.70 (s, 3H), 3.89 (s, 3H), 7.17 (t, J = 7.8 Hz, 1H), 7.58 (dd, J = 7.8, 1.5 Hz, 1H), 7.78 (dd , J = 7.8, 1.5Hz, 1H) Reference Example 1 8

 2-Methyl-1-3-methyl trifluoromethyl benzoate

3-methyl 2-methylbenzoate (0.80 g, 2.90 t ol) and copper (I) iodide (0.12 g, 0.63 t ol) are suspended in 5 ml of dimethylformamide, and fluorosulfonyl is added. (Difluoro) Methyl acetate (1.0 ml, 7.91 mmol) was added, and the mixture was stirred at 80 ° C for 6 hours under an argon atmosphere. After allowing to cool, copper (I) iodide (0.18 g, 0.95 mmol) and methyl fluorosulfonyl (difluoro) acetate (2.0 ml, 15.8 alcohol) were added, and the mixture was stirred at 80 ° C for 10 hours. After completion of the reaction, pentane was added to the reaction solution, and the precipitate was separated by filtration. The filtrate was washed twice with water and once with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. The solvent was concentrated to give the title compound (0.62 g) as a colorless transparent oil.

CI-MS (m / z); 219 (M '+ 1), EI-S (m / z); 218 (Μ ^÷ )

'.Eta. thigh _{(<J, CDC1 3);} 2.64 (s, 3H), 3.93 (s, 3H), 7.34 (dd, J = 7.8, 8.1Ηζ, IH), 7.77 (d, J = 8.1Hz, IH ), 7.91 (d, J = 7.8Hz, lH) Reference example 1 9

 2-bromomethyl-3-methyl trimethylsilylethynylbenzoate

 Methyl 2-methyl-3-trimethylsilylethynylbenzoate (1.05 g, 4.26 octol) was dissolved in 15 ml of acetonitrile, and N-bromosuccinic acid imide (0.87 g, 4.89 mmol) and benzoyl peroxide (0.22 g, 0.68), and the mixture was heated and refluxed for 6 hours under an argon atmosphere.

 After completion of the reaction, hexane was added to the reaction solution, which was washed sequentially with water, a saturated aqueous solution of sodium hydrogen carbonate and an aqueous solution of saturated sodium chloride, and dried over anhydrous sodium sulfate. The solvent was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: hexane / ethyl acetate == 99.5 / 0.5 (volume ratio)) to give 1.02 g of the title compound as a pale yellow oil. Obtained.

CI-MS (m / z); 325 (Μ * + 1), EI-MS (m / z); 324 (M +)

'.Eta. thigh _{(S, CDC1 3); 3.95} (s, 3H), 5.19 (s, 2H), 7.31 (t, J = 7.87Hz, IH), 7.63 (dd, J = 7.8, 1.5Hz, IH) , 7.89 (dd, J = 7.8, 1.5 Hz, IH) In the same manner as in Reference Example 19, the following compound of Reference Example 20 was obtained. Reference Example 20

 2-bromomethyl-3-trifluoromethyl benzoate

Properties: colorless transparent oil

CI-MS (m / z); 297 (Μ * + 1), EI-MS (m / z); 217 (M ⁴ -Br)

¾- Anonymous _{(S, CDC1 3); 3.99} (s, 3H), 5.11 (s, 2H), 7.49 (dd, J = 8.1, 7.6Hz, 1H), 7.82 (d, J = 8.1Hz, IH), 8.05 (d, J = 7.6Hz, lH) reference example 14 in the same manner as (c), _c reference example 2 1 to give the compound of the following reference examples 2 1-24

 2- [4-1-[(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] phenoxymethyl] methyl 3--3-ethynylbenzoate

Properties: yellow solid

CI-MS (m / z); 456 (Μ * + 1), EI-MS (m / z); 455 (Μ ⁺ )

'Η-丽 (5, CDC); 3.33 (s, lH), 3.80 (s, 3H), 5.59 (s, 2H), 6.99-7.02 (m, 2H), 7.21 (d, J = 16.4Hz, 1H), 7.40 (t, J = 7.8H _Z) lH), 7.49 (dd, J = 10.0, 8.3Hz, IH), 7.56-7.59 (m, 2H), 7.60 (dJ = 8.8Hz, IH), 7.70 (dd, J = 7.8,1.2Hz, IH), 7.76-7.83 (m, 2H) ₍ 8.02 (dJ = 8.8Hz, IH) Reference example 22

 2- [4-1-[(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] phenoxymethyl] -13-methyl trifluoromethylbenzoate

Properties: yellow solid

 CI-MS (m / z); 500 (M * + l), EI-MS (m / z); 499 (Μ ')

 -Thigh "); 3.77 (s, 3H), 5.46 (s, 2H), 6.97-7.00 (m, 2H), 7.22 (d, J = 16.4Hz, IH), 7.50 (dd, J = 10.0, 8.3Hz) , lH), 7.57-7.60 (m, 2H), 7.61 (dd, J = 8.1, 7.8Hz, IH), 7.68 (d, J = 16.1Hz, IH), 7.80 (dd, J = 11.5, 7.8Hz, lH), 7.86 (dJ = 8.1Hz, IH), 7.95 (d, J = 7.8Hz, IH), 8.03 (d, J = 8.5Hz, IH) Reference Example 23

 3-fluoro-2_ [4— [(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] phenoxymethyl] ethyl benzoate

Properties: yellow solid

 CI-MS (ra / z); 464 (MVl), EI-MS (m / z); 463 (Μ ')

'H- _{丽, CDC1 3); 1.18 (t} , J = 7.1Hz, 3H), 4.23 (q, J = 7.1Ηζ, 2H), 5.37 (s, 2H), 7.06 (d, J = 8.8Hz, 2H ), 7.34 (d, J = 16.4Hz, IH), 7.51-7.72 (m, 5H), 7.81 (d, J = 16.4Hz, IH), 7.86-8.05 (m, 3H), 8.34 (d, J = (8.8Hz, IH) Reference example 24

 3-Fluoro-2- [4-[(E) —2- (7-Chloro-6-fluoro-2-quinolinyl) ethenyl] phenoxymethyl] ethyl ethyl benzoate

Properties: yellow solid

CI-MS (m / z); 480 (M '+ 1) ₎ EI-MS (m / z); 479 (Μ')

'H - _{thighs, CDC1 3): 1.18 (tJ} = 7.1Hz, 3H), 4.23 (q, J = 7.1Hz, 2H), 5.37 (s, 2H), 7.06 (d, J = 8.8Hz, 2H), 7.34 (d, J = 16.1Hz, IH), 7.55-7.72 (m, 5H), 7.81 (d, J = 16.4Hz, IH), 7.91 (d, J = 8.8Hz, IH), 7.98 (d, J = 9.8Hz, 1H), 8.19 (d, J = 7.3Hz, IH), 8.35 (d, J = 8.8Hz, IH) In the same manner as in Reference Example 14 (d), the following Reference Examples 25 to 28 Was obtained. Reference Example 2 5

 2-[(E) 1 2— (6,7-difluoro-2-quinolinyl) ethenyl] 1 7-ethynyl-6,11-dihydrodibenz [b, e] oxepin 1 1-one

Properties: yellow solid

CI-MS (m / z); 424 (NT + 1), EI-MS (m / z); 423 (Μ ') 'Η-wake (S.DMSO- d ₆ ); 3.47 (s, lH), 5.56 (s, 2H), 7.21 (d, J = 8.5 Hz, IH), 7.44 (d, J = 16.4 Ηζ, ΙΗ) , 7.58 (t, J = 7,8Hz, IH), 7.79 (dd, J = 7.8, 1.5Hz, 1H), 7.84 (dd, J = 7.8, 1.5Hz, IH), 7.92 (d, J = 16.4Hz , IH), 7.94-8.09 (in, 3H), 8.31 (d, J = 2.4 Hz, IH), 8.38 (d, J = 8.6 Hz, IH) Reference Example 26

 2— [(E) — 2— (6,7-difluoro-2-quinolinyl) ethenyl] 1,6,11-dihydro 7-trifluoromethyldibenz [b, e] oxepin-1 1 1-one

Properties: yellow solid

 CI-MS (ra / z); 468 (Μ '+ 1), EI-MS (m / z); 467 (M *)

'.Eta. s _{Awakening, CDC1 3); 5.41 (s} , 2H), 7.14 (d, J = 8.54Hz, IH), 7.33 (d, J = 16.4Hz, 1H), 7.51 (dd, J = 10.3, 8.3Hz , IH), 7.59 (t, J = 7.8 Hz, lH), 7.62 (d, J = 8.8 Hz, IH), 7.73 (d, J = 16.4 Hz, IH), 7.81 (dd, J = 8.5, 2.4 Hz , LH), 7.82 (dd, J = 11.5, 7.6Hz, IH), 7.91 (d, J = 7.8Hz, IH), 8.00 (d, J = 7.81Hz, IH), 8.07 (d, J = 8.6Hz , IH), 8.39 (d, J = 2.4Hz, IH) Reference Example 2 7

 7-Fluoro-2 -— ((E) -1-2- (6,7-Difluoro-2-quinolinyl) ethenyl) -1,6,11-dihydrobenz [b, e] oxepin

Properties: yellow solid

 CI-MS (ni / z); 418 (M '+ 1), EI-MS (m / z); 417 (*)

'H-NMR (5, CDC1 3); 5.45 (s, 2H), 7.22 (d, J = 8.5Hz, IH), 7.45 (d, J = 16.4Hz, IH), 7.57-7.64 (m, 3H) , 7.95 (d, J = 16.ΙΗζ, ΙΗ), 8.00-8.09 (m, 4H), 8.34 (d, J = 2.2Hz, IH), 8.42 (d, J = 8.8Hz, IH) Reference example 2 8

 7-Fluoro-2-[(E) -2- (7-chloro-6-fluoro-2-quinolinyl) ethenyl] 1-6,11-dihydrodibenz [b, e] oxepin-1 1-one

Properties: yellow solid

 CI-MS (m / z); 434 (M '+ 1), EI-MS (m / z); 433 (M *)

'Eta - thigh _{(S, CDC1 3); 5.45} (s, 2H), 6.83 (d, J = 8.5Hz, IH), 7.24 (d, J = 16.4Hz, IH), 7.42-7.78 (m, 3H) , 7.76 (d, J = 16.6 Hz, lH), 7.88-8.32 (ra, 4H), 8.34 (d, J = 2.9 Hz, 1H), 8.39 (d, J = 8.3 Hz, IH) Reference example 1 4 ( By the same method as in e), the following compounds of Reference Examples 29 to 32 were obtained. Reference Example 29

 2— [(E) 1 2— (6,7-difluoro-2-quinolinyl) ethenyl] 1 7-ethynyl-1 1-hydroxy-1 6,11-dihydroxybenz [b, e] oxepin

Properties: yellow solid

CI-S (m / z); 426 (Μ * + 1), EI-MS (m / z); 425 (Μ ') '.Eta. thigh (O _{ヽ, CDC1 3); 2.83 (d} , J = 4.4Hz, lH), 3.36 (s, lH), 5.55 (d, J = 13.7Hz, IH), 5.76 (d, J = 4.6 Hz, 1H), 5.95 (d, J = 13.9 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 7.23 (d, J = 15.4 Hz, IH), 7.30 (d, J = 7.6 Hz, IH), 7.43-7.68 (m, 7H), 7.79 (dd, J = ll.2, 7.6Hz, IH), 8.04 (d, J = 8.6Hz, IH) Reference example 30

 2-((E) 1 2 _ (6,7-difluoro-2-quinolinyl) ethenyl) _ 1 1-hydroxy 1, 6,11-dihydro 7 7-trifluoromethyldibenz [b, e] oxepin

Properties: yellow solid

 CI-MS (m / z); 470 (M * + 1), EI-MS (m / z); 469 (Μ ')

'.Eta. thigh _{(S, CDC1 3); 2.82} (s, IH), 5.43 (d, J = 13.9Hz, IH), 5.86 (s, lH), 6.12 (d, J = 13.7Hz, IH), 6.97 (d, J = 8.5Hz, IH), 7.23 (d, J = 15.1Hz, IH), 7.41-7.71 (ra, 8H), 7.78 (dd, J = ll.2, 7.8Hz, IH), 8.04 ( d, J = 8.6Hz, IH) Reference example 3 1

 7-Fluoro-2-[((E) —2— (6,7-Difluoro-2-quinolinyl) ethenyl] 1 1 1-Hydroxy-1 6,11-Dihydrodibenz [b, e] oxepin

Properties: yellow solid

CI-MS (m / z); 420 (M ^, +1), EI-MS (m / z); 419 (Μ ^÷ )

Thigh _{(S, CDC1 3); 5.46} (dJ = 13.2Hz, IH), 5.71 (d, J = 14.6Hz, IH), 6.03 (d, J = 4.2Hz, IH), 6.42 (d, J = 4.2Hz , IH), 6.87 (d, J = 8.5Hz, IH), 7.21-7.42 (m, 3H), 7.32 (d, J = 16. IHz, IH), 7.59 (d, J = 8.5Hz, lH), 7.77-7.83 (m, IH), 7.89 (d, J = 9. OHz, IH), 7.97 (d, J = 9. OHz, IH), 8.03 (d, J = ll. OHz, IH), 8.34 ( d, J = 8.8Hz, IH) Reference example 32

 7—Full-year 2 — [(E) —2— (7—Black 1—6-fluoro-2-quinolinyl) ethenyl] 1 1 1—Hydroxy-1 6,11—Dihydrodibenz [b, e Oxepin

Properties: yellow solid

 CI-MS (ra / z); 436 (M '+ 1), EI-MS (ra / z); 435 (Μ')

'H-NMR (δ, CDC1 3); 5.47 (d, J = 12.7Hz, IH), 5.68 (d, J = 12.7Hz, IH), 6.05 (s, lH), 6.88 (d, J = 8.5Hz , IH), 7.21- 7.42 (m, 4H), 7.39 (d, J = 16.1 Hz, IH), 7.57 (m, IH), 7.82 (s, IH), 7.98 (d, J = 8.8 Hz, IH) , 8.02 (d, J = 9.8Hz, IH), 8.21 (d, J = 7.3Hz, IH), 8.40 (d, J = 8.5Hz, IH) Reference example 33

 2-[(tetrahydropyran-1-2-yl) oxy] 1,6,11 dihydrodibenz [b, e] oxepin 1 1 1 1

2-hydroxy-1,6-dihydroxybenzenes [b, e] oxepin-11-one (9.95 g, 44.0 ol) was dissolved in 100 ml of ethyl acetate, and dihydropyran (25.0 ml, 274.0 mraol) was added. p—torue Pyridinium sulfonate (2.llg 8.4 ol) was added, and the mixture was stirred at room temperature for 21 hours.

 After the reaction was completed, ethyl acetate was added to the reaction solution, and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate and then with a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. The solvent was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: ethyl hexane acetate = 97Z5 (volume ratio)) to obtain 12.45 g of the title compound as a pale yellow solid.

CI-MS (m / z); 311 (M '+ 1), EI-MS (m / z); 226 (M * -THP)

 'H-NMRiiJ.CDClj); 1.59-1.73 (m, 3H), 1.84-2.04 (in, 3H), 3.64 (dt, J = ll.5, 4.4 Hz.lH), 3.93 (ddd J = 11.5,9.0 3.2Hz lH), 5.15 (s, 2H), 5.42 (t, J = 3.3Hz, 1H), 9.98 (d, J = 8.8Hz, 1H), 7.22 (dd, J = 8.8 3.2Hz, 1H) 7.33 ( dd J = 7.3, 1.5Hz, 1H) 7.45 (dt J = 7.6, 1.5Hz 1H)

7.54 (dt J = 7.6 1.5Hz lH), 7.89 (d J = 3.2Hz 1H), 7.92 (dd, J = 7.8, 1.5Hz, 1H) Reference example 34

 1 1—Hydroxy 2-((tetrahydropyran-1-2-yl) oxy) 1 1 1 — [(2-Trimethylsilyl) ethynyl] 1,6,11-Dihydroxybenz [be] oxepin

 N-Butyllithium 1.6M hexane solution (80.0ml) in a 50ml solution of trimethylacetylene (20.0ml, 142.0mmol) , 128.0 mmol) was added dropwise over 20 minutes. After stirring for 10 minutes, 2-[(tetrahydropyran-1-2-yl) oxy] -1,6-dihydroxybenzene [be] oxepin-11-one (29.lg 93.8 ol) is dissolved in 200 ml of tetrahydrofuran The solution was added and stirred at the same temperature for 1 hour, and further stirred at room temperature for 2 hours.

 After completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was concentrated to give the title compound (38.3 g) as a pale yellow solid (a mixture of diastereoisomers).

CI-MS (m / z); 409 (M ++ 1), EI-MS (m / z); 408 (Μ '), 324 (Μ'-THP)

'H-NMR (0 \ CDC1 ₃ ); 0.30 (s 3H), 1.59-1.67 (m, 3H), 1.79-2.03 (m, 3H), 3.55-3.59 (m, 1H),

3.86- 3.93 (m lH), 4.26 (s 0.5H) 4.30 (s, 0.5H), 5.24 (dJ = 14.4 Hz, 0.5H) 5.25 (d, J = 14.7Hz, 1H), 5.31- 5.35 (m, 1H), 5.67 (d J = 14.4Hz, 0.5H), 5.69 (d J = 14.7Hz, 0.5H), 6.93-6.95 (m, 2H), 7.05-7.08 (m, lH), 7.25-7.30 (m , 2H), 7.66-7.69 (m, 1H), 8.09-8.12 (m, 1H) Reference example 3 5

 1 1-Ethynyl- 1 1-Hydroxy-1 2-((tetrahydro-pyran-1-2-yl) oxy) 1 6 11 Dihydrodibenz [b, e] oxepin

 1 1-Hydroxy-2-((tetrahydropyran-1-yl) oxy) 1 1 1 1 ((2-trimethylsilyl) ethynyl) -1 6 11-Dihydroxybenz [be] oxepin (38.3 g 93.8 mmol) Was dissolved in 200 ml of tetrahydrofuran, and a 1.0 M solution of tetra-n-butylammonium fluoride (95.0 ml, 95.0 mmol) in tetrahydrofuran was added, followed by stirring at room temperature for 40 minutes.

After the reaction, add water to the reaction solution, extract with ethyl acetate, and wash the organic layer with saturated aqueous sodium chloride. Washed with the solution and dried over anhydrous sodium sulfate. The solvent was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: toluene / ethyl acetate = 99.5 / 0.5 (volume ratio)) to obtain 26.2 g of the title compound as a white solid (diastereo). Mixture of isomers).

CI-MS (m / z); 319 (Μ'-0H), 252 (NT- THP), EI-MS (m / z); 252 (M THP)

'H-wake, CDC; 1.57-1.71 (ra, 3H), 1.81-2.01 (m, 3H), 3.06 (s, 0.5H), 3.07 (s, 0.5H), 3.56- 3.60 (m, 1Η), 3.86- 3.90 (m, IH), 4.21 (br.s, IH), 5.29 (d, J = 14.7Hz, 0.5H), 5.30 (d, J = 14.9Hz, 0.5H), 5.33- 5.34 (m, lH), 5.47 (d, J = 14.9Hz, 0.5H), 5.53 (d, J = 14.9Hz, 0.5H), 6.96-6.98 (in, 2H), 7.04-7.07 (m, IH), 7.25-7.31 (m, 2H), 7.60-7.62 (m, IH), 8.09-8.12 (m, IH) Reference example 3 6

 2— [2-Hydroxy-1-6,11-Dihydroxybenz [b, e] oxepin-1-111-Ilidene] Acetaldehyde

 1 1-Ethynyl 1 1 1-Hydroxy-1 2-((tetrahydrobiran-1-2-yl) oxy) 1-6,11 Dihydrodibenz [b, e] Oxepin (0.80 g, 2.4 recitation 01) in tetrahydrofuran It was dissolved in 10 ml and 2 ml of distilled water was added. To this mixture was added trifluoroacetic acid (0.4 ml, 5.2 described ol), and the mixture was stirred at room temperature for 18 hours.

 After completion of the reaction, a saturated aqueous solution of sodium hydrogen carbonate was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: toluene / ethyl acetate = 9-1 (volume ratio)) to obtain 0.42 g of the title compound as a yellow solid (mixture of geometric isomers) ).

CI-MS (m / z); 253 (M '+ 1), EI-MS (m / z); 252 (M *)

'H-NMR (0 \ CDC1 3); 4.91 (br, lH), 5.18 (s, 2H), 6.32 (d, J = 7.8Hz, 0.67H), 6.58 (d, J = 8.3Hz, 0.33H) , 6.71-6.89 (m, 3H), 7.24-7.45 (in, 4H), 9.57 (d, J = 8.1Hz, 0.33H), 9.88 (d, J = 7.8Hz, 0.67H) Reference example 3 7

 4- [2-Hydroxy-6,11-dihydroxybenz [b, e] oxepin-11-ylidene] -12-Ethyl butenoate

 Triethyl phosphonoacetate (11. Oral, 55.4 mmol) was added to a mixture of 60% oily sodium hydride (2.04 g, 51.0 mmol) and 20 ml of tetrahydrofuran, and the mixture was stirred at room temperature for 15 minutes. 2-hydroxy-1,6-dihydroxybenz [b, e] oxepin-1-1-ylidene] Acetaldehyde (3.57 g, 14.2 mmol) dissolved in 20 ml of tetrahydrofuran is added, and further added at room temperature. Stirred for minutes.

After the completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction solution, extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: hexane / ethyl acetate = 85/15 (volume ratio)) to give 3.71 g of the title compound as a yellow solid (geometric isomer mixture) ). CI-MS (m / z); 323 (M '+ 1), EI-MS (m / z); 322 (*)

'H- Awakening: _{(S, CDC1 3); 1.26} (t, J = 7.1Hz, 0.33H), 1.29 (. T, J = 7 lHz, 0.66H), 4.18 (q, J = 7.08Hz, 0.33H) , 4.22 (q, J = 7.1Hz, 0.66H), 5.13 (s, 2H), 5.27 (br, 0.33H), 5.61 (br, 0.66H), 6.06 (dd, J = 15.4, 0.7Hz, 0.33H ), 6.08 (dd, J = 15.4, 1.0Hz, 0.66H), 6, 45 (dd, J = ll.7, 1.0Hz, 0.66H), 6.68-6.85 (m, 3.33H), 7.22-7.45 ( ra, 4H), 7.41 (dd, J = 15.4, 11.7Hz, 0.33H), 7.76 (dd, J = 15.4, 11.7Hz, 0.66H) Reference Example 38

 4— [2-Hydroxy-6,11-Dihydroxybenz [b, e] oxepin-111] Ethyl butanoate

 41- [2-Hydroxy-6,11 dihydrodibenz [b, e] oxepin-11-ylidene] — Platinum oxide obtained by dissolving ethyl 2-butenoate (0.50 g, 1.6 ramol) in 5 ml of ethanol (IV) 10 mg was suspended in 2 ml of ethanol and added, followed by stirring at room temperature for 42 hours under a hydrogen atmosphere.

 After completion of the reaction, insolubles were removed by filtration from the reaction solution, and the filtrate was concentrated to obtain 0.51 g of the title compound as a colorless transparent oil.

 CI-S (m / z); 327 +1), EI-MS (m / z); 326 (Μ ')

'H-NMR (<5, CDC1 3); 1.22 (t, J = 7.1Hz, 3H), 1.55 (quintet, J = 7.8Hz, 2H), 1.96-2.08 (ra, 1H),

2.17-2.30 (m, 1H), 2.26 (t, J = 7.6Hz, 2H), 3.64 (t, J = 7.7Hz, 1H), 4.09 (q, J = 7.1Hz, 2H),

4.96 (d, J = 15.1 Hz, lH), 5.04 (br, lH), 5.39 (d, J = 15.1 Hz, 1H), 6.61-6.65 (m, 2H), 6.90-6.93 (m, 1H), 6.97 -7.00 (m, 1H), 7.13-7.18 (m, 3H) Reference example 39

 6, 7-difluoro-2-vinylquinoline

 6,7-Difluoro-1-methylquinoline (10.64 g, 59.4 octol) was dissolved in a mixture of 8 ml of ethanol and triethylamine (0.2 ml, 1.4 ol) and 37% formaldehyde (4.72 g,

 59.4) and stirred at 60 ° C for 2 hours. Then, a mixture of getylamine hydrochloride (6.60 g, 59.4 mmol), ethanol 3 ml, water 3 ml and triethylamine (0.4 ml, 2.8 ol) was added over 30 minutes, and then added at 60 ° C. Stirred for hours.

 After completion of the reaction, water was added to the reaction solution, and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent was concentrated and the resulting residue was subjected to silica gel chromatography (eluent: hexane / ethyl acetate = 9Z1 (volume ratio)) to give the title compound.

2.89 g were obtained as a pale yellow solid.

 CI-MS (m / z); 192 (M '+ 1), EI-S (m / z); 191 (Μ')

'H-NMR (δ, DMS0 -d 6); 5.69 (dd, J = ll.0, 1. OHz, 1H), 6.39 (dd, J = 17.6, 1.0Hz, 1H), 6.95 (dd, = 17.6 , 11.0Hz ₍ 1H), 7.82 (d, J = 8.8Hz, 1H), 6.93 (dd, J = 8.1, 3.9Hz, 1H), 8.00 (dd, J = 9.0, 2.2Hz, 1H), 8.33 (d , J = 8.5Hz, 1H) Reference example 40

 1 1-oxo-1 2-trifluoromethanesulfonyloxy 6,11-dihydrodibenz [b, e]

 Dissolve 2-hydroxy-6,11-dihydroxybenz [b, e] cepin_11-one (1.12g, 4.6mmol) in methylene chloride (20ml) and add trifluoromethanesulfonic anhydride under ice-cooling. (2.32 mL, 13.8 mL) and triethylamine (1.84 mL, 13.8 mL) were added, and the mixture was stirred at the same temperature for 6 hours.

 After completion of the reaction, the reaction solution was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: toluene Z-ethyl acetate = 9/1 (volume ratio)) to obtain 0.95 g of the title compound as a black oil. . CI-MS (ra / z); 375 (M '+ 1), EI-MS (m / z); 374 (ΝΓ)

'Η-wake, DMS0-d ₆ ); 4.35 (s, 2H), 7.40-7.50 (m, 2H), 7.53 (d, J = 7.8Hz, 1H), 7.58 (d, J = 7.3Hz, 1H) , 7.60-7.70 (m, 2H), 8.08 (d, J = 2.2 Hz, 1H) In the same manner as in Reference Example 40, the following compound of Reference Example 41 was obtained. Reference example 4 1

 5-oxo-1 3-trifluoromethanesulfonyloxy 1 0,11-dihydro-5 H-dibenzo [a, d] cycloheptene

Properties; brown oil

 CI-MS (ra / z); 357 (Ml), EI-MS (m / z); 356 (M *)

'.Eta.赚_{(<J, DMS0- d 6)} ; 3,00-3.30 (m, 4H), 7.30-7.50 (ra, 3H), 7.51-7.65 (m, 2H), 7.70 (dd, J = 8.5 , 2.7Hz, lH), 7.88 (d, J = 2.9Hz, 1H) Reference example 42

 2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1,6,11-dihydrodibenz [b, e]

 1 1-year-old 2-oxo-trifluoromethanesulfonyloxy 6,11-dihydrobenz [b, e] cepin-2-yl (0.67 g, 1.8 mmol) and 6,7-difluoro-2-vinyl Quinoline (0.31 g, 1.6 ol) was dissolved in 7 ml of N, N-dimethylformamide, and palladium acetate (0.04 g, 0.2 ol). Trifdinylphosphine (0.16 g, 0.6 ol) and bromide. Lithium (0.84 g, 4.8 t ol) was added. Then, in a nitrogen atmosphere, triethylamine (2.01111, 14.0 bandages 01) was added, and the mixture was stirred at 100 ° C for 4 hours.

 After completion of the reaction, the reaction solution was concentrated, and the obtained residue was subjected to silica gel chromatography (eluent: toluene / ethyl acetate = 9Z1 (volume ratio)) to obtain 0.62 g of the title compound as a brown solid. CI-MS (ra / z); 416 (M ++ 1), EI-MS (m / z); 415 (Μ ')

'Η-encomment (S, DMS0- d ₆ ); 4.31 (s, 2H), 7.30-8.20 (in, 11H), 8.32 (dJ = 7.8Hz, 1H), 8.39 (d, J = 8.5Hz, 1H) The following compound of Reference Example 43 was obtained in the same manner as in Reference Example 42. Reference example 4 3

 3-[(E) -2- (6,7-difluoro-2-quinolinyl) ethenyl] 1-10,11-dihydro-5H-dibenzo [a, d] cyclohepten-5-one

Properties; brown solid

 CI-MS (m / z); 398 (M '+ 1), EI-MS (m / z); 397 (M *)

'H-NMR (-5, DMSO-d ₆ ); 3.21 (s, 4H), 7.20-7.55 (m, 7H), 7.85-8.25 (ra, 5H), 8.38 (d, J = 8.5Hz, 1H) The following compounds of Reference Examples 44 to 45 were obtained in the same manner as in Reference Example 1 (b). Reference example 44

 2 -— [(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl) 1-11-hydroxy-1,6,11-dihydrodibenz [b, e] cepin

Properties: brown solid

 CI-MS (m / z); 418 (Μ * + 1), EI-MS (m / z); 417 (Μ ')

'Eta - thigh _{(S, DMS0- d 6);} 4.38 (d, J = 13.7, 1H), 4.68 (d, J = 13.7Hz, 1H), 6.21 (s, 1H), 7.06 (d, J = 8.3 Hz, 1H), 7.20-7.50 (m, 5H), 7.34 (d, J = 14.9, 1H), 7.84 (d, J = 14.4, 1H), 7.90-8.15 (m, 4H), 8.40 (d, J = 8.8Hz, 1H) Reference example 4 5

 3 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 5-hydroxy-10, U-dihydro-5H-dibenzo [a, d] cycloheptene

Properties: brown solid

CI-MS (m / z); 400 (Μ * + 1), EI-MS (m / z); 399 (M *)

'Η-thigh (, DMS0- d ₆ ); 3.00-3.30 (m, 4H), 5.90-6.05 (br.s, 1H), 6.13 (s, lH), 7.10-7.60 (m, 6H), 7.39 ( d, J = 16.4Hz, lH), 7.65-8.10 (m, 5H), 8.35 (d, J = 8.8Hz, 1H) Reference example 46

 8-bromo-1,2,11-dihydroxy-6,11-dihydroxybenz [b, e] oxepi

Dissolve 8-bromo-1-hydroxy-1,6,11-dihydrodibenz [b, e] oxepin-11-one (48.41 g, 0.159 mol) in a mixture of 400 ml of tetrahydrofuran and 200 ml of methanol. Sodium borohydride (6.00 g, 0.159 mol) was added, and the mixture was stirred at room temperature for 2 hours.

After completion of the reaction, the solvent was distilled off under reduced pressure, water was added to the residue, the pH was adjusted to about 6.0 with 1N-hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 55.95 g of the title compound as a dark brown oil. This This compound was used in the next reaction of Reference Example 47 without purification.

CI-MS (ra / z); 307 (MVl), EI-MS (m / z); 306 (Μ ')

'Η-thigh, DMS0_d ₆ ); 5,52 (d, J = 13,7 Hz, lH), 5.30 (d, J = 13.7 Hz, IH), 5.91 (d, J = 4. Hz, IH), 6.12 (d, J = 4.6Hz, IH), 6.57 (dd, J = 8.8, 2.9Hz, IH), 6.68 (d, J = 8.8Hz, IH),

6.84 (d, J = 2.9Hz, IH), 7.40-7.60 (m, 3H), 9.01 (s, lH) Reference example 47.

 8-promo 2-hydroxy 1 1 1-methoxy 6,11-dihydroxybenz [b, e] oxepin

 After dissolving 8-bromo-1,2,1-dihydroxy-1,6,11-dihydroxybenz [b, e] oxepin (55.95 g) in 500 ml of methanol, p-toluenesulfonic acid monohydrate ( 3.02 g, 15.9 ol) were added and the mixture was heated under reflux for 1.5 hours.

 After completion of the reaction, the solvent was distilled off under reduced pressure, and the obtained residue was subjected to silica gel chromatography (gradient eluent: hexane to ethyl hexanenoacetate = 91 (by volume)) to give 45.85 g of the title compound. Obtained as a brown oil.

CI-MS (m / z); 321 (M ^, +1), EI-MS (m / z); 320)

 'H-NMR .DMSO-); 3.25 (s, 3H), 4.95 (d, J = 12.9 Hz, IH), 5.16 (s, lH), 5.57 (d, J = 12.9 Hz, IH), 6.67 (dd , J = 8.8, 2.2Hz, IH), 6.69 (d, J = 8.lHz, IH), 6.74 (dJ = 2.OHz, IH), 7.39 (d, J = 8.3Hz, IH), 7.52 (dd , J = 8.1, 2.2 Hz, IH), 7.61 (d, J = 2. OHz, IH) Reference example 48

 8-Promo 2-t-Butyldimethylsilyloxy 1 1 1-Methoxy-6,11 Dihydrodibenz [b, e] oxepin

 8-Bromo-2-hydroxyl 11-Methoxy-6,11 dihydroxybenz [b, e] oxepin (41.75 g, 0.130 mol) is dissolved in methylene chloride (400 ml), and t-butyldimethylsilyl chloride is dissolved. (29.78 g, 0.198 mol), imidazole (17.88 g, 0.263 mol) and N, N-dimethylaminoviridine (1.59 g, 0.013 mol) were added, and the mixture was stirred at room temperature for 1.5 hours.

 After completion of the reaction, the solvent was distilled off under reduced pressure, and the obtained residue was subjected to silica gel chromatography (gradient eluent: hexane to hexane / ethyl acetate-50 / 1 (volume ratio)) to give 51.26 g of the title compound. Was obtained as a red oil.

CI-MS (m / z); 435 (Ml), EI-MS (m / z); 434 (Μ ^÷ )

¾-NMR, DMS0_d ₆ ); 0.16 (s, 6H), 0.94 (s, 9H), 3.24 (s, 3H), 4.96 (d, J = 12.7 Hz, IH), 5.20 (s, lH), 5.66 ( d, J = 12.5Hz, lH), 6.65-6.75 (m, IH), 6.76 (dJ = 8.8Hz, IH), 6.84 (d, J = 2.0Hz, IH), 7.38 (d, J = 8.3Hz, IH), 7.55 (dd, J = 8.1, 2.2Hz, IH), 7.66 (d, J = 2.OHz, IH) Reference example 49

1 1-Methoxy-1 8-Methoxycarbonyl-2-t-butyldimethylsilyloxy 6, 1 1 dihydrobenz [b, e] oxepin

 8-Bromo-11-Methoxy-2-t-butyldimethylsilyloxy-6,11 dihydrodibenz [b, e] oxepin (5.00 g, 11.48 mmol) in a solution of 60 ml of tetrahydrofuran at 1 78 ° C Then, a n-butyllithium 2.52M hexane solution (6.83 ml, 17.22 mmol) was added dropwise, and the mixture was stirred at the same temperature for 30 minutes. Next, dry ice (65.0 g) was gradually added, and the temperature was slowly raised to room temperature. Then, dimethyl sulfate (1.30 ml, 13.78 mmol) was added, and the mixture was heated under reflux for 8.5 hours. After completion of the reaction, ethyl acetate was added to the reaction solution, washed with a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 5.44 g of the title compound. Obtained as a red-brown oil. This product was used in the next reaction of Reference Example 50 without further purification.

 CI-MS (ra / z); 415 (M * + 1), EI-MS (m / z); 414 (M *)

'Eta - thigh _{(S.DMSO- d 6); 0.16 (} s, 6H), 0.94 (s, 9H), 3.28 (s, 3H), 3.87 (s, 3H), 5.11 (d, J = 12.5Hz, 1H), 5.34 (s, 1H), 5.70 (d, J = 12.7Hz, 1H), 6.72 (d, J = 8.8Hz, 1H), 6.76 (d, J = 8, 8Hz, 1H), 6.87 (d , J = 2.0Hz, lH), 7.58 (d, J = 7.8Hz, lH), 7.94 (dd, J = 7.8, 1.7Hz, 1H), 8.00 (d, J = 2.0Hz, 1H) Reference example 50

 2—Hydroxy-1 1 1-Methoxy 1 8—Methoxycarbonyl 6,11—Dihydroxybenz [b, e] oxepin

 1 1-Methoxy-1-8-Methoxycarbonyl-2-t-butyldimethylsilyloxy-6,11-Dihydroxybenz [b, e] oxepin (5.44 g) in 250 ml of tetrahydrofuran, ice-cooled Below, tetra-n-butylammonium fluoride (6.00 ml, 20.66 mmol) was added, and the mixture was stirred at the same temperature for 1 hour.

 After the completion of the reaction, a saturated aqueous solution of ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was subjected to silica gel chromatography (gradient eluent: toluene to toluene Z-ethyl acetate = 73 (volume ratio)) to give 2.47 g of the title compound as a yellow oil. As obtained. CI-MS (m / z); 301 (M '+ 1), EI-MS (m / z); 300 ()

'Η-spirit, DMSO- d ₆ ); 3.29 (s, 3H), 3.86 (s, 3H), 5.10 (dJ = 12.9Hz, 1H), 5.31 (s, lH), 5.61 (d, J = 12.7Hz , 1H), 6.66 (dd, J = 8.8, 2.4Hz, lH), 6.70 (d, J = 8.1Hz, 1H), 6.77 (d, J = 2.4Hz, 1H), 7.59 (d, J = 7.8Hz , 1H), 7.92 (dd, J = 7.8, 1.7Hz, 1H), 7.95 (d, J = 1.7Hz, 1H), 9.06 (Br.s.1H) Method similar to Example 5 1 (b) As a result, the following compound of Reference Example 51 was obtained. Reference example 5 1

 1 1-Methoxy 8-1-Methoxycarbonyl 2-Trifluoromethanesulfonyloxy 6,1 1-Dihydrobenzenes [b, e] oxepin

CI-MS (m / z); 433 (Ml), EI-MS (ra / z); 432 (M *) 'Eta - thigh (d _{ヽ, DMSO- d c); 3.32 (} s, 3H), 3.88 (s, 3H), 5.30 (d, J = 12.5Hz, 1H), 5.56 (s, lH), 5.80 (d , J = 12.5Hz, lH), 6.98 (d, J = 9.0Hz, lH), 7.38 (dd, J = 9.0, 3.2Hz, 1H), 7.58 (d, J = 2.9Hz, 1H), 7.58 (d , J = 8.3 Hz, lH), 7.99 (dd, J = 7.8, 1.7 Hz, 1H), 8.08 (d, J = 1.7 Hz, 1H) The following method was used in the same manner as in Example 5 1 (c). The compound of Reference Example 52 was obtained. Reference Example 52

2-[(E) -2-(5,6,7,8-tetrahydro-2-quinolinyl) ethenyl]-1 1 1-methoxy-8-methoxycarbonyl-1 6,11-dihydrodibenz [b, e Oxepin CI-MS (m / z); 442 (Μ ⁺ +1), EI-MS (m / z); 441 (M *)

'.Eta. thigh _{(S.DMSO- d 6); 1.60-1.90 (} m, 2H), 2.72 (t, J = 6.1Hz, 1H), 2.81 (t, J = 6.3Hz, 1H),

3.29 (s, 3H), 3.86 (s, 3H), 5.16 (d, J = 12.5Hz, 1H), 5.36 (s, 1H), 5.86 (d, J = 12.2Hz, 1H), 6.82 (d, J = 8.5Hz, 1H), 7.10 (d, J = 16.1Hz, 1H), 7.26 (d, J = 8.lHz, 1H), 7.41 (d, J = 8.lHz, 1H), 7.48 (d, J = 16.1 Hz, lH), 7.53 (dd, J = 8.5, 2.2 Hz, 1H), 7 · 58 (d, J = 8. lHz, 1H), 7.68 (d, J = 2.0 Hz, 1H), 7.96 ( dd, J = 7.8,1.7Hz ₎ 1H), 8.05 (d, J = l.7Hz, 1H) Reference example 53

 9-1 [(E)-2- (6,7-Difluoro-2-quinolinyl) ethenyl] —6,1 1 Dihydrodibenz [b, e] oxepin-1 1-one

 9-Bromo-6,11-Dihydroxybenz [b, e] oxepin-1-1-one (2.0g,

6.9 mmol) and 6,7-difluoro-2-vinylquinoline (l, 58 g, 8.3 mmol) in 40 ml of N, N-dimethylformamide were added to palladium acetate (0.67 g, 3.0 mmol) and triphenylphosphine (0.33 mmol). g, 13 mmol), and then triethylamine (6.0 ml, 42 mmol) was added under a nitrogen atmosphere, followed by stirring at 100 ° C. for 4 hours.

 After completion of the reaction, water was added to the reaction solution, extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The residue obtained by concentrating the solvent was subjected to silica gel column chromatography (eluent: hexane / ethyl acetate = 31 (volume ratio)) to obtain 0.97 g of the title compound as an ocher solid.

 CI-MS (m / z); 400 (M '+ 1), EI-MS (m / z); 399 (Μ')

'H-NMR (δ, DMS0 -d 6); 5.34 (s, 2H), 7.14 (. D, J = 9 ΟΗζ, 1H), 7.20 (t, J = 8.1Hz, 1H), 7.57-7.67

(m, 3H), 7.91- 8.08 (m, 6H), 8.14 (ddj = 8.1, 1.7Hz, 1H), 8.40 (d, J = 8.6Hz, 1H) In the same manner as in Reference Example 1 (b), The following compound of Reference Example 54 was obtained. Reference example 54

9-[(E)-2-(6,7-difluoro-2-quinolinyl) ethenyl] — 11-hydroxy-6,11 dihydrodibenz [b, e] oxepin Properties: ocher solid

 CI-S (m / z); 402 (M * + 1), EI-MS (m / z); 401 (Μ ')

'H-NMR (δ, DMS0-d _fl ); 5.24 (d, J = 12.7 Hz, 1H), 5.71 (d, J = 12.5 Hz, 1H), 5.92 (s, lH), 6.21 (br.s, 1H), 6.39 (dJ = 9.3Hz, 1H), 6.93 (t, J = 7.6Hz, 1H), 7.18 (tJ = 8.3Hz, 1H), 7.42-7.52 (m, 3H), 7.66 (dJ = 7.8 Hz, lH), 7.84-8.27 (m, 5H), 8.38 (dj = 8.6Hz, 1H) Reference example 5 5

 5—Fluoroquinaldine

Croton aldehyde (23.5 ml, 0.28 mol) was added dropwise over a period of 50 minutes to a mixed solution of 3-fluoroaniline (30.0 g, 0.27 mol) in 40 ml of water and 145 ml of concentrated hydrochloric acid under heating and refluxing, and heated for 2 hours Refluxed.

 After the completion of the reaction, the reaction solution was cooled and washed with methylene chloride. Then, toluene was added to the aqueous layer, the pH was adjusted to about 9.0 with a 30% aqueous sodium hydroxide solution, and the mixture was extracted with toluene. The organic layer is washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated, and the residue obtained is subjected to silica gel column chromatography (gradient eluent: toluene to toluene ethyl acetate = 10/1 (volume ratio). )) To give 1.04 g of the title compound as a yellow oil. CI-MS (m / z); 162 (Μ * + 1), EI-MS (m / z); 161 (M

 'H-NMR (δ, DMSO-d,); 2.69 (s, 3H), 7.37 (ddd, J = 10.0, 7.8, 1. OHz, 1H), 7.52 (d, J = 8.8Hz, 1H), 7.71 (td, J = 7.8, 6.1Hz, 1H), 7.80 (d, J = 8.5Hz, 1H), 8.37 (d, J = 8.5Hz, 1H) Reference Example 56

 2-bromomethyl-5-fluoroquinoline

To a solution of 5-fluoroquinaldine (2.03 g, 12.6 mmol) in 40 ml of ethyl acetate, add N-bromosuccinate imide (4.05 g, 22.8 mmol) and 2,2'-azobis (isobutyronitrile) (0.37 g, (25.25 mmol) in several portions while heating under reflux for 12 hours.

 After completion of the reaction, the reaction solution is cooled, washed with a saturated aqueous solution of sodium hydrogencarbonate, an aqueous solution of sodium thiosulfate, and then with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated, and the residue obtained is subjected to silica gel column chromatography. (Eluent: hexane Z ethyl acetate = 50/1 (volume ratio)) to give 2.20 g of the title compound as a yellow solid.

CI-MS (m / z); 240 (M ^÷ + 1), EI-MS (m / z); 239 (Μ ')

 'Η-thigh (δ, DMSO-de); 4.89 (s, 2H), 7.47 (ddd, J = 10.0, 7.8,1. OHz, 1H), 7.79 (d, J = 8.8Hz, 1H), 7.75- 7.85 (m, 1H), 7.88 (d, J = 8.5Hz, 1H), 8.54 (d, J = 8.5Hz, 1H) Reference Example 57

 (5-Fluoroquinoline-2-yl) triphenylphosphonium bromide

To a solution of 2-bromomethyl-5-fluoroquinoline (2.20 g, 9.2 mmol) in 15 ml of acetonitrile was added triphenylphosphine (3.36 g, I2.81M0I), and the mixture was heated and stirred at TC for 5 hours. After completion of the reaction, the solvent was distilled off from the reaction solution under reduced pressure, and the residue was crystallized by adding getyl ether, and filtered. The obtained crystals were washed with getyl ether and dried under reduced pressure to give the title compound (5.46 g). Was obtained as a brown solid.

CI-MS (m / z) ; 421 (M'-HBr), EI-MS (m / z); by 421 (M ⁴ -HBr) similar to Reference Example 55 method, the following Reference Examples 58 to 60 The compound was obtained. Reference Example 58

 5, 7—difluoroquinaldine

Properties; brown solid

CI-MS (m / z); 180 (Μ ^÷ +1), EI-MS (ra / z); 179 (M *)

'Η-thigh (S, DMS0-d ₆ ); 2.69 (s, 3H), 7.40-7.60 (m, 3H), 8.34 (d, J = 8.8 Hz, IH) Reference example 59

 5, 6, 7—Trifluoroquinaldine

Properties; brown solid

CI-MS (m / z); 198 (M '+ 1), EI-MS (m / z); 197 (M ⁺ )

 'Η-thigh (ό ヽ, DMS0-); 2.68 (s, 3H), 7.56 (d, J = 8.5Hz, IH), 7.81 (ddd, J = ll.7, 7.1, 2.4Hz, IH), 8.38 (d, J = 8.8Hz, IH) Reference example 60

 6-fluoro-7-trifluoromethylquinaldine

Properties; brown solid

CI-MS (m / z); 230 (M '+ 1), EI-MS (m / z); 229 (Μ ^÷ )

'H-NMR (S, DMS0 -d 6); 2.87 (s, 3H), 7.89 (d, J = 8.8Ηζ, IH), 8.28 (d, J = ll.2Hz, IH),

8.66 (d, J = 6.8 Hz, IH), 8.70 (d, J = 8.5 Hz, IH) By the same method as in Reference Example 56, the following compounds of Reference Examples 61 to 63 were obtained. Reference example 6 1

 2-bromomethyl-5,7-difluoroquinaldine

Properties; brown solid

CI-MS (m / z); 180 (M '+ 1), EI-MS (m / z); 179 (Μ ⁺ )

'.Eta. thigh _{(0,, DMS0-d 6} ); 4.87 (s, 2H), 7.55-7.75 (m, 2H), 7.76 (d, J = 8.8Hz, IH), 8.53 (d, J = 8.5Hz , IH)

Reference Example 62

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 L 9 f ^ 呦 I 9 Stop deprivation ΥΓ1,, (A T ¾ ^ teaching fe |? Z fl ^ 08

*Country :

 Λ t α, mu γ 9 9 Γι QS (mM) 6 £ V: (z / m) SW_I3 '(ュ 9H- + W) 6: (z / i) SW-13 Λ ^ a ^ Ma <· τφ: Φ ^ T um 4 Ι ~ Z-^ ί ^ ^ ~ Λ (LA-L '9' S)

昍-) 6S: (z / «i) SW-13 '(m-M) & £: (z / ui) sw_D

^ t π, ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^

 V 9 Γι ^ ST

. ^ ·?呦 ^ 9 9 ~ 9 9 ^ Poison 丄, Τ Γ 1Γ ^ ^ # | ^ ^ Z S

0Τ 'Ρ) Ζ 8' (Ηΐ

0Τ

(J) 08 :( ² / w) SW- 13 '(ΐ + Qin 0 £: (z / m) SW- D

 '.Transition ε 9 Poison

(Ηΐ 'zH8'8 = f' P) 9S'8

'(Ηΐ''lΊ' Z 'S' Π = Γ 'PPP) S6 Ί' (Ηΐ 'ΖΗ8' 8 = Γ 'P) C8' L '(HZ' s) 88 ': ( ⁹ P- OS' S) 丽-H,

 (J) 6 T: (z / ui) SW-13 '(ΐ + »Μ) 08ΐ: (z / ui) SW-13

 • ^ rn: translation

90t60 / 00df / X3d 688 0 ΟΛΧ (b) 2-((E)-2-(6,7-Difluoro-2-quinolinyl) ethenyl) 1 7-Fluoro 1 1-Hydroxy-1,6,1 1-Dihydrodibenz [b, e] oxepin

Properties: light yellow solid

E - thigh _{(5, DMS0-d 6)} ; 8.35 (d, J = 8.6Hz, lH), 8.05-7.29 (ra, 9H), 7.18 (tdJ = 9.0, 2.7Hz, IH), 6.84 (d, J = 8.5Hz, 1H), 6.25 (br.s, IH), 5.93 (s, lH), 5.73 (d, J = 12.5Hz, IH), 5.27 (d, J = 12.5Hz, IH) Reference example 1 9 The following compound of Reference Example 68 was obtained in the same manner as in the above. Reference Example 68

 2-bromomethyl-4-ethyl benzoate

Properties: reddish brown oil

CI-MS (m / z); 261 (M '+ 1)

 'Η-thigh (, CDC13); 8.02 (dd, J = 4.3, 2.7Hz, IH), 7.19 (dd, J = 9.3, 2.7Hz, IH),

7.05 (td, J = 7.8, 2.7 Hz, lH), 4.93 (s, 2H), 4.40 (q, J = 7.1 Hz, 2H), 1 · 42 (t, J = 7.1 Hz, 3H) Reference example 14 ( By the same method as in c), the following compound of Reference Example 69 was obtained. Reference Example 69

 2- (4-difluoroquinoline-2-ylethenyl) phenoxymethyl I-4-1ethyl ethyl benzoate

Properties: light yellow solid

CI-MS (m / z); 464 (M '+ l)

 'Η-thigh (S'DMSO-de); 8.35-7.06 (ra, 13H), 5.48 (S, 2H), 4.30 (q, J = 7.1Hz, 2H), 1.30 (t, J = 7.IHz, 3H) The following compound of Reference Example 70 was obtained in the same manner as in Reference Example 14 (d). Reference example 70

 2— I 4-(6,7—difluoroquinoline-1- 2-ylhetenyl) pheno

Fluorobenzoic acid

Properties: yellow solid

CI-MS (m / z); 436 (Μ * + 1)

 'Η-thigh (δ, DMSO-de); 8.34-6.92 (m, 13H), 5.52 (S, 2H)

Claims

 The scope of the claims  -General formula (I)

In the formula, R ¹ is a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a carboxy group, a C—C ₄ alkoxycarbonyl group, a 1 H-tetrazo-1-yl 5-yl group , A C, —C ₄ alkyl group, a fluoro C ₄ alkyl group, a hydroxy C, —C ₄ alkyl group, a C ₂ —C ₄ alkenyl group, a C ₂ —C ₄ alkynyl group, a C, —C ₄ alkoxy group, A fluoro C, —C ₄ alkoxy group, a C! —C ₄ alkylthio group, a C ^ —C alkylsulfinyl group or a C, —C ,, alkylsulfonyl group; R ² represents a hydrogen atom, a halogen atom, Represents a nitrogen atom, a cyano group, a C _t -C ₄ alkyl group or a C i -C ₄ alkoxy group, and A represents 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom. 5 or 6-membered heteroaromatic ring group including Indicates heteroaromatic fused ring group Kowamoto and a benzene ring are condensed, complex-aromatic ring group or heteroaromatic fused ring group as substituent, C androgenic atom, a nitro group, Shiano group, - C ₄ alkyl group, A fluoro C 1, 1 C ₄ alkyl group, a C, —C ₄ alkoxy group, a fluoro C, — (4 alkoxy group, a Ci—C ₄ alkylthio group, a fluoro C, 1 alkylthio group or a C ₃ —C ₄ alkylene group; B may represent the formula — OCH ₂ —, the formula — CH ₂ CH ₂ —, the formula — S CH ₂ —, the formula —CH ₂ 0 — or the formula —CH ₂ S—, and X represents an oxygen atom , A sulfur atom, a methylene group or a formula = CH—, and Y is a C, — which may have a halogen atom, a C 1, —C ₄ alkyl group or a C, 1-C ₄ alkoxy group as a substituent. C, an alkylene group, a phenylene group or a group of the formula (a):

Wherein o and p each represent an integer of 0 to 2, q represents an integer of 1 to 4, and Z represents an optionally protected carboxy group; 1 H-tetrazole-1-yl group ; formula - S0 ₃ H group; formula - NH- S0 ₂ - R ^3; or wherein one CO- NH- S 0 ₂ - R ³ In the formula, R ³ represents a C, —C ₄ alkyl group, a fluoro C, —C ₄ alkyl group or a halogen atom as a substituent, a C, —C ₄ alkyl group, a fluoro-1C ₄ alkyl group, a 1 (: ₄ Group consisting of alkoxy, fluoro C, —C alkoxy, nitro and cyano Represents a phenyl group optionally having at least one substituent selected from the group consisting of: represents a single bond or a double bond And m represents an integer of 1 to 4, and when m is 2 or more, R ′ may be different, n represents an integer of 1 to 3, and when n is 2 or more, R ² represents Or a pharmacologically acceptable salt thereof, which may be different. 2. In the compound represented by the formula (I), R ¹ is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a hydroxyl group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a carboxy group, or a methoxycarbonyl group. Group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, 1H-tetrazol-5-yl group, methyl group, ethyl group, propyl group, isopropyl group, fluoromethyl group, difluoromethyl group, trifluoromethyl group Group, 2-fluoroethyl group, hydroxymethyl group, 1-hydroxyxyl group, 2-hydroxyxyl group, 1-hydroxy-1-1-methylethyl group, 1-hydroxypropyl group, 2-hydroxypropyl group, vinyl Group, 1-propenyl group, aryl group, 1-butenyl group, 2-butenyl group, 2-methyl_1-probe Nyl, ethynyl, 1-propynyl, 1-butynyl, methoxy, ethoxy, propoxy, isopropoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy From methylthio, ethylthio, propylthio, isopropylthio, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, methylsulfonyl, ethylsulfonyl, propylsulfonyl and isopropylsulfonyl The tricyclic compound or a pharmaceutically acceptable salt thereof according to claim 1, which is selected from the group consisting of: 3. In the compound represented by the formula (I), R ¹ is a hydrogen atom, a fluorine atom, a chlorine atom, a hydroxyl group, a nitro group, a cyano group, a carbamoyl group, a formyl group, a methoxycarbonyl group, or an ethoxycarbonyl group. , 1H-tetrazo-1-yl 5-methyl, methyl, ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, 1-hydroxyl, 1-hydroxy-1-methylethyl Group, 1-hydroxypropyl group, vinyl group, 1-propenyl group, aryl group, ethynyl group, 1-propynyl group, 1-butynyl group, methoxy group, ethoxy group, fluoromethoxy group, difluorome Toxyl group, trifluoromethoxy group, methylthio group, ethylthio group, methylsulfinyl group, ethylsulfinyl group, methylsulfur Cycloalkenyl Moto及 Pi E Ji Rusuruhoniru tricyclic compound or a pharmacologically acceptable salt thereof of claims any preceding claim in which selected from the group consisting of groups. 4. In the compound represented by the formula (I), R ¹ is a hydrogen atom, a fluorine atom, a nitro group, a cyano group, a formyl group, a methoxycarbonyl group, a 1H-tetrazol-15-yl group, a methyl group. Group, difluoromethyl group, trifluoromethyl group, hydroxymethyl group, 1-hydroxy-1- 1-methyl 2. The method according to claim 1, which is selected from the group consisting of a tyl group, a vinyl group, an ethynyl group, a methoxy group, a difluoromethoxy group, a trifluoromethoxy group, a methylthio group, a methylsulfinyl group, and a methylsulfonyl group. Or a pharmacologically acceptable salt thereof. 5. The compound according to claim ¹ , wherein R ^{1 of the} compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a cyano group, a trifluoromethyl group and an ethinyl group. Or a pharmacologically acceptable salt thereof. 6. R ^{2 of the} compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a nitro group, a cyano group, a methyl group, an ethyl group, a methoxy group and an ethoxy group. 3. The tricyclic compound according to claim 1, or a pharmaceutically acceptable salt thereof. 7. The tricyclic ring according to claim 1, wherein R ^{2 of the} compound represented by the formula (I) is selected from the group consisting of a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group and a methoxy group. Or a pharmacologically acceptable salt thereof. 8. The tricyclic compound or the pharmaceutically acceptable salt thereof according to claim 1, wherein R ^{2 of the} compound represented by the formula (I) is a hydrogen atom. 9. In the compound represented by the formula (I), the ring represented by A is furan, thiophene, oxazole, thiazole, imidazole, pyrazole, thiadiazole, pyridine, pyrimidine, pyridazine, pyrazine, benzofuran, benzothiophene, The tricyclic compound according to claim 1, which is selected from the group consisting of benzoxazole, benzothiazole, benzimidazole, quinoline, quinazoline and a quinoxaline ring, or a pharmaceutically acceptable tricyclic compound thereof. salt. 10. In the compound represented by the formula (I), the ring represented by A is oxazole, thiazole, imidazole, pyrazole, thiadiazol, pyridine, pyrimidine, pyridazine, pyrazine, benzoxazole, benzothiazol. The tricyclic compound according to claim 1, which is selected from the group consisting of benzimidazole, quinoline, quinazoline and a quinoxaline ring, or a pharmaceutically acceptable salt thereof. 1 1. In the compound represented by the formula (I), the ring represented by A is selected from the group consisting of thiazole, thiadiazole, pyridine, pyrimidine, benzoxazole, benzothiazol, quinoline and quinazoline rings. 3. The tricyclic compound according to claim 1 or a pharmacologically acceptable salt thereof. 12. The tricyclic compound or the tricyclic compound according to claim 1, wherein the ring represented by A in the compound represented by the formula (I) is selected from the group consisting of pyridine, benzothiazole and quinoline rings. Its pharmacologically acceptable salts. 13. The above heteroaromatic ring group or heteroaromatic condensed ring group is selected from the group consisting of fluorine, chlorine, bromine, nitro, cyano, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, fluoromethyl, difluoromethyl, trifluoromethyl From the fluoromethyl, 2-fluoroethyl, methoxy, ethoxy, propoxy, isopropoxy, fluoromethoxy, difluromethoxy, trifluoromethyl, 2-fluoroethoxy, methylthio, ethylthio, propylthio, isopropylthio, trimethylene and tetramethylene groups The tricyclic compound or a pharmaceutically acceptable salt thereof according to any one of claims 9 to 12, which is substituted with at least one selected substituent. 14. The heteroaromatic ring group or heteroaromatic condensed ring group is a fluorine atom, a chlorine atom, nitro, cyano, methyl, ethyl, isopropyl, t-butyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, fluoromethoxy, difluorome. The compound according to any one of claims 9 to 12, wherein the compound is substituted by at least one substituent selected from toxic, trifluoromethoxy, methylthio, ethylthio, trimethylene, and tetramethylene groups. Tricyclic compounds or pharmacologically acceptable salts thereof. 15. The above heteroaromatic ring group or heteroaromatic condensed ring group is selected from the group consisting of fluorine, chlorine atom, nitro, cyano, methyl, isopropyl, t-butyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, and methylthio. And the tricyclic compound according to any one of claims 9 to 12 or a pharmacologically acceptable salt thereof, wherein the tricyclic compound is substituted by at least one substituent selected from a tetramethylene group. Salt. 16. The method according to claim 9, wherein said heteroaromatic ring group or heteroaromatic condensed ring group is substituted with at least one substituent selected from fluorine, chlorine atom, trifluoromethyl and tetramethylene. Or the pharmacologically acceptable salt thereof according to any one of Items 1 to 12. 17. A of the compound represented by the formula (I) is 2-oxazolyl, 2-thiazolyl, 2- or 4- imidazolyl, 3-pyrazolyl, 1,3,4-thiadiazol-2-yl, 2 — pyridyl, 2 — or 4 — pyrimidinyl, 3 — pyridazinyl, 2 — pyrazinyl, 2 — benzoxazolyl, 2- benzothiazolyl, 2 — benzimidazolyl, quinoline 1 2 — yl, quinazoline 1 2 — i Quinoxaline-1-yl, quinolizine-3-yl, 4-methyl-2-thiazolyl, 4-ethyl-2-thiazolyl, 4-isopropyl-12-thiazolyl, 4-t- Butyl-1-2-thiazolyl, 4 _trifluoromethyl-1-2-thiazolyl, 5 _methyl-1,3, 4 —thiadiazole— 2 —yl, 5-ethylethyl 1,3,4-thiadiazol 1 —yl, 5-isopropyl-1, 3,4 —thiadiazol 1-2 —yl, 5-t-butyl 1,3,4-thiadiazol-2-yl, 5—trifluoromethyl-1,3,4—thiadiazol-2-yl, 5,6-difluoro-2-pyridyl, 5,6-dichloro Mouth 2-pyridyl, 5,6-dimethyl-2-pyridyl, 5, 6-Jethyl-12-pyridyl, 6-trifluoromethyl-12-pyridyl, 6-methylthio-12-pyridyl, 5, 6- Dihydrocyclopenta [b] pyridine-1-2-yl, 5,6,7,8-tetrahydroquinoline-12-yl, 5,6-difluoro-2-pyrimidinyl, 5,6-dichloro-2-pyrimidinyl, 5, 6-Dimethyl-2-pyrimidinyl, 6_trifluoromethyl-1-2-pi Midinyl, 5,6-dihydrocyclopentene [d] pyrimidin-1-yl, 5,6,7,8-tetrahydroquinazoline-12-yl, 6-fluoro-2-benzoxazolyl, 5— Fluoro-2-benzobenzozolyl, 5,6-difluoro-2-benzobenzozolyl, 6-chloro-2-benzobenzoxazolyl, 5-chloro-1-benzobenzosazolyl, 5,6-dichloro-2- Benzoxazolyl, 5-chloro-6-fluoro-2-benzobenzozolyl, 5-methyl-1-benzobenzoxazolyl, 5-cyano_2-benzoxosazolyl, 5-trifluoromethyl-2-benzobenzoxazolyl, 5-Methylthio-1-benzoxazolyl, 6-Fluoro-2-benzothiazolyl, 5-Fluoro-2-benzothiazolyl, 5, 6-Difluoro-2-benzothiazolyl, 6_ Roro 2 - benzothiazolyl, 5 — Cloth — benzothiazolyl, 5,6-dichloro-2 — benzothiazolyl, 5-chloro — 6 — Fluoro — 2 — benzothiazolyl, 5-methyl — 2 — benzothiazolyl, 5 — cyano 2 — benzothiazolyl, 5- trifluoro Romethyl_2-benzothiazolyl, 5-methylthio_2_benzothiazolyl, 5-fluoroquinolin-1-yl, 6-fluoroquinoline-2-yl, 7-fluoroquinolin-1-yl, 5-cloquinoline-2 _Yl, 6—black mouth quinoline-2-yl, 7—black mouth quinoline_2—yl, 7—methylquinoline 1-2—yl, 7—trifluoromethylquinoline 1-2_yl, 7 —Methoxyquinoline 1-2-yl, 7-difluoro methoxyquinoline 1-2 —yl, 7 —Trifluorome toxic quinoline 1-2 —yl, 5, 7, 7-difluoroquinoline 1-2 —Yl, 6, 7—Difluoroquinoline 1 2 —yl, 5, 7—Dichloro quinoline 1 2 —yl, 6, 7—Dichloroquinoline 1 2 —yl, 5 —Chloro 7—fluoro Quinoline 1 2 — yl, 6 — Black mouth 7 _ Fluoroquinoline 1 2 _yl, 7 — Black mouth 1 5 — Fluoroquinoline 1 2 — yl, 7 — Black mouth 1 6 — Fluoroquinoline _ 2 — 7 —Black mouth 6 —Cyanokinoline 1 2 —yl, 7 —Cyano_ 6 —Fluoroquinoline 1 2 —yl, 6—Fluorol 7 _Trifluoromethylquinoline 1 —2, 5, 6, 7 _ Trifluoroquinoline 1 2 _yl, 5 — Fluoroquinazoline 1 2 — yl, 6 — Fluoroquinazoline 1 2 — yl, 7 — Fluoroquinazoline 1 2 — yl, 5 — Black mouth Quinazoline 1 2 — yl, 6 — black quinazoline 1 2 — yl, 7 — black quinazoline 1 2 — yl, 7 — Tylquinazoline 1-2-yl, 7-Trifluoromethylquinazoline 1-2-yl, 7-Methoxyquinazoline 1-2-yl, 7-Difluoro methoxyquinazoline 1-2-yl, 7-Trifluoromethoxy Quinazoline 1 2 — yl, 5, 7—Difluoroquinazoline 1 2 —yl, 6,7—Difluoroquinazoline 1 2 —yl, 5,7-Dichloroquinazolin 1 2 —yl, 6, 7—Dichloroquinazoline 1 2— 5-, chloro-7-fluoroquinazoline 1 2 _yl, 6-black 1 7-fluoroquinazoline 1-yl, 7-chloro 5 -fluoroquinazoline 1-2, 7-black 1-6—Fluoroquinazoline 1 2—yl, 7—Chloro 6—Cyanokinazoline 1 2—yl, 7—Cyano 1 6—Fluoroquinazoline 1 2—yl, 6—Fluoro 1 7—Triflu 3. The tricyclic compound according to claim 1, wherein the tricyclic compound is selected from the group consisting of o-methylquinazoline_2-yl and 5,6,7-trifluoroquinazoline-2-yl groups or Its pharmacologically acceptable salts. 1 8. A of the compound represented by the formula (I) is 2-thiazolyl, 1,3,4-thiadiazole-2-yl, 2-pyridyl, 2-pyrimidinyl, 2-benzoxazolyl, 2- Benzothiazolyl, quinolin-1-yl, quinazoline-1-yl, 4-methyl-2-thiazolyl, 4-isopropyl-2 2-thiazolyl, 4_t-butyl-1-2_thiazolyl, 4-trifluoro Methyl-1-thiazolyl, 5-methyl-1,3,4-thiadiazole-2-yl, 5-isopropyl-1--1,3,4-thiadiazole-1-yl, 5-t-butyl-1,3,4- Thiadiazole—2—yl, 5—Trifluoromethyl-1,3,4—thiadiazol-1-2—yl, 5,6-difluoro-2-pyridyl, 5, 6—dichloro-1-pyridyl, 5, 6—Dimethyl-2-pyridyl, 5, 6—Dihydrocyclopentene [b] Pyridine-1-yl, 5,6,7,8-tetrahydroquinoline-12-yl, 5,6-difluoro-2-pyrimidinyl, 5,6-dichloro-2-pyrimidinyl, 5,6-dimethyl-1-yl 2-pyrimidinyl, 6-trifluoromethyl-2-pyrimidinyl, 5,6-dihydrocyclopenta [d] pyrimidine-1-yl, 5,6,7,8-tetrahidroquinazoline_2-yl , 6 -Fluoro-2-benzobenzoxazolyl, 5 -Fluoro-2-benzobenzozolyl, 5, 6-Difluoro-2-benzobenzozolyl, 6 -Chloro-2-benzobenzozolyl, 5 -Chloroox 2 —Benzoxazolyl, 5,6-dichloro-1-2-benzoxazolyl, 5-chloro-6—fluoro-2-benzobenzoxolyl, 5-methyl-2-benzobenzoxazolyl, 5-cyano-2-benzobenzozoli 5 Rifluoromethyl-1-benzobenzozolyl, 5-methylthio-2-benzobenzozolyl, 6-fluoro-2-benzobenzothiazolyl, 5-fluoro-2-benzothiazolyl, 5,6-difluoro-2-benzothiazolyl, 6-chloro- 2-benzothiazolyl, 5-chloro-2-benzothiazolyl, 5, 6-dichloro-1-benzothiazolyl, 5-chloro-6-fluoro-2-benzothiazolyl, 5-methyl-1-benzothiazolyl, 5-cyano_2-benzothiazolyl, 5 —Trifluoromethyl-2-benzothiazolyl, 5-methylthio-1-2-benzothiazolyl, 5 —Fluoroquinoline-1-yl, 6 —Fluoroquinoline 1-2 —yl, 7—Fluoroquinoline 1-2 —yl, 5 —Chloroquinoline 1 2-yl, 6-black quinoline _ 2-yl, 7-black quinoline 1-yl, 7-methylquinoline 1-2-yl, 7-trifluoromethylquinoline_2-yl, 7-methoxyquinoline 1-2-yl, 7-difluoromethoxyquinoline 1-2_yl , 7-trifluoroquinoline-1-2-yl, 5, 7-difluoroquinoline-1-2-yl, 6, 7-diph L-loquinoline 1 2 _yl, 5,7-dichloro mouth quinoline 1 2 —yl, 6,7-dichloroquinoline 1 2 _yl, 5 —chloro-7 —fluoroquinoline 1 2 —yl, 6 —black mouth 1 7 — Fluoro mouth quinoline 1-2-yl, 7 _ Black mouth 1-Fluoroquinoline 1-2-yl, 7-Black mouth _ 6-Fluoroquinoline 1-2-yl, 7-Chloro 6-cyanoquinoline 1-2-ィ7-Cyanol 6-Fluoroquinoline 1-2-yl, 6_Fluoro-7-Trifluoromethylquinoline 1-2-yl, 5, 6, 7-Trifluoroquinoline 1-2-yl, 5-Fluoro Lokinazoline 1 2 — yl, 6 — Fluoroquinazoline 1 2 — yl, 7 — Fluoroquinazoline 1 2 — yl, 5 — Chloroquinazoline 1 2 — yl, 6 — Black mouth quinazoline 1 2 _yl, 7 — Black mouth quinazoline 1 2 —Ill, 7—Methylquinazoline 1-2—yl, 7—Trifluoromethylquinazoline 1-2—yl, 7—Methoxyquinazoline 1-2—yl, 7—Difluoromethoxyquinazoline 1-2—yl, 7—Trifluoromethoxy Quinazoline-1-yl, 5,7-Difluoroquinazoline-1-yl, 6,7-Difluoroquinazolin-1-yl, 5,7-Dicloquinonequinazole-2-yl, 6 , 7-Dichloroquinazoline 1- 2-yl, 5--Chloro 7-Fluoroquinazoline- 1- 2-yl, 6-Chloro 7-Fluoro-quinazoline 1-2-yl, 7-Chloro-5-Fluoro Quinazoline-1 2 —yl, 7—chloro-6-fluoroquinazoline 1-2 —yl, 7—black mouth 6—cyanoquinazoline 1-2 —yl, 7 —cyano 6 —fluoroquinazoline 1 2 —Yl, 6 —Fluoro-7—Trifluorometylquinazoline The tricyclic compound according to claim 1, which is selected from the group consisting of 2-yl and 5,6,7-trifluoro-2-azoline-1-2-yl groups, or a pharmacologically acceptable compound thereof. salt. 1 9. A of the compound represented by the formula (I) is 2-pyridyl, 2-benzothiazolyl, quinolin-1-yl, 5,6-difluoro-2-pyridyl, 5,6-diclo-2-pyridyl , Five, 6-dimethyl-1-pyridyl, 5,6,7,8-tetrahydroquinoline-1-yl, 6-fluoro-2-benzothiazolyl, 5-fluoro-2-benzothiazolyl, 5,6-difluo —Benzothiazolyl, 6 —Chloro-2 —benzothiazolyl, 5 _Chloro-2-benzothiazolyl, 5,6—Dichloro-1 —Benzothiazolyl, 5 —Chloro-6 —Fluoro-2-benzothiazolyl, 5 —Methyl-1 2 —Venzothiazolyl, 5—Cyanol 2—Venzothiazolyl, 5—Trifluoromethyl-2-benzothiazolyl, 5-Methylthio-1-2-benzothiazolyl, 5 —Fluoroquinoline 1-2 —yl, 6 —Fluoroquinoline 1-2 —yl 7-Fluoroquinoline 1-2-yl, 5_Chloroquinoline 1-2-yl, 6-Chloroquinoline 1-2_yl, 7-Chloroquinoline_2—Y 7-Methylquinoline 1-2-yl, 7-Trifluoromethylquinoline 1-2-yl, 7-Methoxyquinoline 1-2-yl, 7-Difluoromethoxyquinoline 1-2-yl, 7— Trifluoroquinoline 1-2-yl, 5,7-difluoroquinoline 1-2-yl, 6,7-difluoroquinoline 1-2-yl, 5,7-dichloroquinoline 1-2-yl, 6, 7-dichloroquinoline-1-yl, 5-chloro-1- 7-fluoroquinoline-2-yl, 6-chloro-7-fluoroquinoline-1-yl, 7_chloro-5-fluoroquinoline-1-2 , 7 — Black mouth 6 — Fluoroquinoline 1 — yl, 7 — Black mouth 6 — Cyanokinoline 1 — 2 Selected from the group consisting of 7-cyano-6-fluoroquinoline-1-yl, 6-fluoro-7-trifluoromethylinyl-2-yl and 5,6,7-trifluoroquinoline-12-yl 2. The bicyclic compound according to claim 1 or a pharmacologically acceptable salt thereof. 20. In the compound represented by the formula (I), A is 7-fluoroquinoline-12-yl, 7-chloroquinoline-12-yl, 6,7-difluoroquinoline-12-yl, 6, 7-dichloroquinoline-2-yl, 7-chloro-6-fluoroquinoline-2-yl, 6-fluoro-7-trifluoromethylquinoline-1-yl and 5,6,7,8-tetrahydroquinoline-1 2. The bicyclic compound or a pharmaceutically acceptable salt thereof according to claim 1, which is selected from the group consisting of 2-yl groups. 21. The method according to any one of claims 1 to 20, wherein B in the formula (I) is a formula _OCH ₂ —, a formula — CH ₂₀ — or a formula — CH ₂ CH ₂ —. Tricyclic compounds or pharmacologically acceptable salts thereof. 22. The tricyclic compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20, wherein X in the formula (I) is a methylene group, a sulfur or an oxygen atom. . 23. In the formula (I), Y is methylene, ethylene, trimethylene, tetramethylene, pentamethylene, 'fluoromethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2, 2-difluoroethylene, 1-methylethylene, 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene, 1-methoxyethylene, 2-methoxyethylene , 1-Fluorotrimethylene, 2-Fluorotrimethylene, 3_Fluorotrimethylene, 1,1-Difluorotrimethylene, 2,2-Difluorotrimethylene, 3,3-Difluorotrimethylene, 1-Methyltrimethylene, 2-Methyltrimethylene Methylene, 1,1-dimethyltrimethylene, 2,2-dimethyltrimethylene Tylene, 3,3-dimethyltrimethylene, 2,2-getyltrimethylene, 2-methoxytrimethylene, 3-methoxytrimethylene, 2,2-dimethoxytrimethylene, 3,3-dimethoxytrimethylene, 1, 2-phenylene, 1,3-phenylene group, a group represented by the formula (a), wherein o = 0, p = 0, q = l, o = 0, p = 1, q = A group with 1, a group with o = 0, p = 1, q = 2, a group with o = l, p = 0, q = l, a group with 0 = 1, p = 1, q = 1, and 2. The tricyclic compound according to claim 1, which is selected from the group consisting of groups wherein 0 = 1, p = 1 and q = 2, or a pharmaceutically acceptable salt thereof. 24. In the formula (I), Y is methylene, ethylene, trimethylene, fluoromethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, 1-methylethylene , 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethyl Len, 1 —fluorotrimethylene, 2 _fluorotrimethylene, 3 —fluorotrimethylene, 1,1 difluorotrimethylene, 2,2 —difluorotrimethylene, 3,3-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1, 1—dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3—dimethyltrimethylene, 1,2-phenylene group, and in the group represented by the formula (a), o = l, p = 0 , q = l, o = l, = 1, q = 1 and 0 = 1, = 1, q = 2 Or a pharmacologically acceptable salt thereof. . 25. In formula (I), Y is methylene, ethylene, trimethylene, difluoromethylene, 1-fluoroethylene, 2-fluoroethylene, 1,1-difluoroethylene, 2,2-difluoroethylene, 1-methylethylene , 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene, 2,2-difluorotrimethylene, 1-methyltrimethylene, 2-methyltrimethylene, 1, In 1-dimethyltrimethylene, 2,2-dimethyltrimethylene, 3,3-dimethyltrimethylene, 1,2-phenylene and the group represented by the formula (a), when o = l, p = 1, q = 1, 2. The tricyclic compound or a pharmacologically acceptable salt thereof according to claim 1, which is selected from the group consisting of a group. 26. In the formula (I), Y is methylene, ethylene, trimethylene, 1-methylethylene, 2-methylethylene, 1,1-dimethylethylene, 2,2-dimethylethylene, 1-ethylethylene, 2-ethylethylene , 1,2-phenylene and a tricyclic ring selected from the group consisting of groups in which o = l, = 1 and q = 1 in the group represented by the formula (a) or a pharmacologically acceptable tricyclic ring thereof. Acceptable salt. . Z in 2 7 formula (I) is carboxy, 1 H- tetrazol Ichiru one 5 - I le, wherein one S 0 ₃ H, methanesulfonyl § amino, ethanesulfonyl § Mino, triflumizole Ruo b methanesulfonyl § Mino, off P-Fluorophenylsulfonylamino, p-fluorophenylsulfonylamino, p-methylphenylsulfonylamino, p-methylphenylsulfonylamino, p-methylphenylsulfonylamino, p-trifluoromethylphenylsulfonylamino ., O — methoxyphenylsulfonylamino, p — methoxyphenylsulfonylamino, p — difluoromethoxyphenylsulfonylamino, p — trifluoromeoxyphenylsulfonylamino, p — ditrophenylsulfonylamino, p — shia Nophenylsulfonylamino, methanesulfonylaminocarbo Ethanesulfonylaminocarbonyl, trifluoromethanesulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, p-fluorophenylsulfonylaminocarbonyl, p-fluorophenylsulfonylaminocarbonyl, 0-methylphenyl Sulfonylaminocarbonyl, p-Methylphenylsulfonylaminocarbonyl, p-Trifluoromethylsulfenylaminocarbonyl, 0-Methoxyphenylsulfonylaminocarbonyl, p-Methoxyphenylsulfonylaminocarbonyl, p —Difluorome Toxifueni The compound is selected from the group consisting of rusulfonylaminocarbonyl, p-trifluoromethoxyphenylsulfonylaminocarbonyl, p-ditrophenylsulfonylaminocarbonyl, and p-cyanophenylsulfonylaminocarbonyl. 3. The tricyclic compound according to item 1 or a pharmacologically acceptable salt thereof. 28. In the formula (I), Z is carboxy, 1 H-tetrazo-l-yl 5-yl, formula 1 S 0 ₃ H, methanesulfonylamino, trifluoromethanesulfonylamino, phenylsulfonylamino, 0- Methylphenylsulfonylamino, p-methylphenylsulfonylamino, methanesulfonylaminocarbonyl, trifluoromethanesulfonylaminocarbonyl, phenylsulfonylaminocarbonyl, 0-methylphenylsulfonylaminocarbonyl and p The tricyclic compound according to claim 1, which is selected from the group consisting of a methylphenylsulfonylaminocarbonyl group, or a pharmacologically acceptable salt thereof. 29. Formula Z is in (I), carboxy, selected from formula one S0 ₃ H, methanesulfonyl § Mino, the group consisting of triflupromazine O b methanesulfonyl § amino, methanesulfonyl § amino carbonyl and Torifuruorome Tan sulfonylamino group 3. The tricyclic compound according to claim 1 or a pharmacologically acceptable salt thereof. 30. The tricyclic compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 5, wherein m in the formula (I) is an integer of 1, 2, or 3. . 3 1. The tricyclic compound according to any one of claims 1 and 6 to 8 or a pharmacologically acceptable salt thereof, wherein n in the formula (I) is an integer of 1 or 2. Salt. 32. A compound represented by the formula (I) is  [2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1-6,11-dihydroxybenz [b, e] oxepin-1 1-yl] oxyacetic acid,  [2 — [(E) —2- (6,7-difluoro-2-quinolinyl) ethenyl] 1,6,11-dihydrobenz [b, e] oxepin-111] thioacetic acid,  3— | [2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1-6,1 1-dihydrodibenz [b, e] oxepin-1 1 1-yl] Propionic acid,  3— | [2 — [(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] 1-6,11-dihydrodibenz [b, e] oxepin-1 1 1-yl] —2—Methylpropionic acid, 3-| [2-[(E) — 2— (6,7-difluoro-2-quinolinyl) ethenyl] 1, 6,1 1 -dihydrodibenz [b, e] oxepin 1 1 1-yl] -2,2-dimethylpropionic acid, 3— | [2-[(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] one 6, 1 I—dihydrodibenz [b, e] oxepin-l 1 _yl] thio i-l 2 _ethylpropionic acid, '  3— | [2 — [(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1 1_yl] —3,3-dimethylpropionic acid,  I 1-[[2 — [(E) —2— (6,7—difluoro — 2—quinolinyl) ethenyl] 1 6, I I-Dihydrobenz [b, e] oxepin-11-yl] thiomethyl] cyclopropyl I-acetic acid,  2-1 (2-[(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1 6, 1 1-dihydrodibenz [b, e] oxepin-1 1 1-yl] benzoic acid,  [2-[((E) -2-(6,7-difluoro-2-quinolinyl) ethenyl]] 1,6,1 1-dihydrobenz [b, e] oxepin-1 1 1-yl] Methanesulfonylacetic acid amine K \  3- [2-[(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1-yl] thio-1 N —Methanesulfonylpropionamide,  2-| [2— [(E) —2— (6,7-difluoro-2-quinolinyl) 2) 1 6, 1 1—Dihydrodibens [b, e] oxepin 1 1 1 1 1] thio 1 ethansulfonate,  4— [2-[(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1-yl] butanoic acid  3-| [2— [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl) 1 7-fluoro 6,1 1 dihydrodibenz [b, e] oxepin 1 1 1-yl Thio i-propionic acid,  I 1-[[2-[(E) — 2- (6,7-difluoro-2-quinolinyl) ethenyl] 1 7-fluoro-6,11-dihydrodibenz [b, e] oxepin-1 1- Thiomethyl] cyclopropyl monoacetic acid,  3-| [2 — [(E) —2— (6,7-difluoro-2-quinolinyl) ethenyl] -1-8-fluoro-6,1 1-dihydrodibenz [b, e] oxepin-1 1 1 —Ill] Cho I propionic acid,  3-| [7-cyanone 2_ ((E) 1 2-(6,7-difluoro-2_quinolinyl) ethenyl) 1-6,11 dihydrobenzenes [b, e] oxepin 1 1 1 Zeo I propionic acid, 3— | [2 — [(E) 1 2— (6,7-Difluoro-2-quinolinyl) ethenyl] 1 7—Trifluoromethyl-6,1 1—Dihydrodibenz [b, e] oxepin 1 1 1-yl) thio I propionic acid, 3—i [ ₇ —ethynyl—2 — [(E) -2- (6-, 7-difluoro-2-quinolinyl) ethenyl] 1-6,11-dihydrodibenz [b, e] oxepin 1 1 1 —Ill] Cho I propionic acid,  3-| [2-[(E) — 2- (7-chloro-6-fluoro-2-quinolinyl) ethenyl] 1,6,1 1-dihydrodibenz [b, e] oxepin _11-yl] thio I propionic acid, 3-| [2-((E) — 2— (7-chloro-6-fluoro-2-quinolinyl) ethenyl) -1 7-fluoro-6,11-dihydrodibenz [b, e] oxepin-1 1 1 Ill] Chi! Pionic acid,  II— [[2 — [(E) —2— (7-chloro-6-fluoro-2-quinolinyl) ethenyl] 1-7-fluoro-6,11 dihydrodibenz [b, e] oxepin 1 1— Thiol) thiol propyl I acetic acid,  3— | [2-[(E) —2— (7-Fluoro-2-quinolinyl) ethenyl] 1,6,1dihydrodibenz [b, e] oxepin-1 1 1-yl] thio I propion Acid,  3— | [2-[(E) —2— (7-Fluoro-2-quinolinyl) ethenyl] 1,6,1 1-Dihydrobenz [b, e] oxepin-1 1 1-yl] One 2-methylpropionic acid,  11-[[2-[(E) -2-(7-chloro-1-6-fluoro-2-quinolinyl) ethenyl]] 1,6,1 1-dihydrodibenz [b, e] oxepin-1 1-yl Thiomethyl] cyclopropyl I-acetic acid,  12 — [(E) -2- (7-chloro-1-2-quinolinyl) ethenyl) 1,6,1 1-dihydrobenz [b, e] oxepin _11-yl I thioacetic acid,  3-| [2 — [((E) 1 2— (7—black 1—2—quinolinyl) ethenyl) 1,6,1 1 dihydrodibenz [b, e] oxepin 1 1 1—yl] Acid,  3-1 (2-((E) 1-2-(7-1-quinolinyl) ethenyl) 1-6, 1 1-Dihydrodibenz [b, e] oxepin-1 1-yl! _2—methylpropionic acid,  11 — [[2-[(E) —2 -— (7-chloro-2-quinolinyl) ethenyl] -1,11-dihydrodibenz [b, e] oxepin-11-yl] thiomethyl] cyclopropyl I acetic acid, 3-1 (2-[(E)-2-(5,6,7,8-tetrahydro-1--2-quinolinyl) ethenyl) 1-6,1 1 dihydrodibenz [b, e] oxepin 1 1 1 1 Thiol] thio I propionic acid, 3-1 (2-[(E) -2-(5,6,7,8-tetrahydro-1--2-quinolinyl) ethenyl) -16,11-dihydrodibenz [ b, e] oxepin-1 1-yl] thio! _2-methylpropionic acid,  | 1— [[2 — [(E) —2— (5,6,7,8-tetrahydro-2-quinolinyl) ethenyl] -1 6,1 1-dihydrodibenz [b, e] oxepin-1 1 1-yl] thiomethyl] cyclopropyl I-acetic acid, 3— | [2 — [(E) —2— (6-fluoro-7-trifluoromethyl-1-2-quinolinyl) ethenyl] -1,6,1 1-dihydrobenz [b, e] oxepin-1 1—1 Zeo I propionic acid, 3-l [3-[(E) -2- (6-, 7-difluoro-2_quinolinyl) ethenyl] 1 1 0,1 1-dihydro_ 5H-dibenz [a, d] cycloheptene-5-yl Zeo I propionic acid,  3— | [3 — [(E) — 2— (6,7-difluoro-2-quinolinyl) ethenyl) 1 10,11—dihydro — 5 H—dibenz [a, d] cycloheptene — 5— Thio] 1-2-methylpropionic acid and 3-| [9-[(E) 1 2— (6,7-difluoro-2-quinolinyl) ethenyl] 1 6, 1 1-Dihydrodibenz [b, e] oxepin 1 1 1-yl] 2. The tricyclic compound or a pharmacologically acceptable salt thereof according to claim 1, which is at least one selected from the group consisting of propionic acid. INTERNATIONAL SEARCH REPORT International application No.  PCT / JP00 / 09406 A. CLASSIFICATION OF SUBJECT MATTER Int.CI ⁷ C07D215 / 12, 14, 18, 405/06, 417/06, 413/06, 409/06, A61K31 / 55, 31/47,  A61P43 / 00, 37/08, 29/00  According to International Patent Classification (IPC) or to both national classification and IPC  B. FIELDS SEARCHED  Minimum documentation searched (classification system followed by classification symbols) Int.CI ⁷ C07D215 / 12, 14, 18, 405/06, 417/06, 413/06, 409/06, A61K31 / 55, 31/47 '  A61P43 / 00, 37/08, 29/00 Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched Electronic data base consulted during the international search (name of data base and, where practicable, search terms used)  REGISTRY (STN), CA (STN), CAOLD (STN), CAPLUS (STN) C. DOCUMENTS CONSIDERED TO BE RELEVANT  Category * Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No.  A EP, 685478, Al (UBE INDUSTRIES, LTD.), --32  06 December, 1995 (06.12.95  & WO, 94/19345, Al & JP, 06-518813, A  & US, 5591752, A & CN, 1117730, A  A EP, 468785, A2 (MERCK FROSST CANADA INC. .-32  29 January, 1992 (29.01.92  & JP, 05-105678, A & US, 5221678, A  A WO, 95/18107, Al (MERCK & CO., INC.), ■ 32  06 July, 1995 (06.07.95)  & JP, 09-507235, A & EP, 737186, Al  & US, 5614632, A & CN, 1139429, A I I Further documents are listed in the continuation of Box C. ι ι See patent family annex.  * Special categories of cited documents: "T" later document published after the international filing date or "A" document defining the general state of the art which is not priority date and not in conflict with ihe application but cited to considered to be of particular relevance understand the principle or theory underlying the invention "E" earlier document but published on or after the international filing "X" document of particular relevance; the claimed invention cannot be date considered novel or cannot be considered to involve an inventive "L" document which may throw doubts on priority cJaim (s) or which is step when the document is taken alone  cited to establish the publication date of another citation or other "Y" document of particular relevance; the claimed invention cannot be special reason (as specified) considered to involve an inventive step when the document is "O" document referring to an oral disclosure, use, exhibition or other combined with one or more other such documents, such  means combination being obvious to a person skilled in the art "P" document published prior to the international filing date but later "&" document member of the same patent family  than the priority date claimed  Date of the actual completion of the international search Date of mailing of the international search report  27 February, 2001 (27.02.01) 13 March, 2001 (13.03.01) Name and mailing address of the ISA / Authorized officer  Japanese Patent Office  Facsimile No. Telephone No.  Form PCT / ISA / 210 (second sheet) (July 1992)